• C. elegans
• PUF RNA-binding protein
• PUF partnerships
• germline stem cells
• sperm/oocyte cell fate decision

• RNA-Binding Proteins/metabolism
• RNA-Binding Proteins/genetics
• Caenorhabditis elegans Proteins/metabolism
• Caenorhabditis elegans Proteins/genetics
• Animals
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans/metabolism
• Stem Cells/metabolism
• Stem Cells/cytology
• Protein Binding
• RNA/metabolism
• RNA/genetics
• Mutation

• P40 OD010440 NIH HHS
• R01 GM050942 NIGMS NIH HHS
• R01 GM134119 NIGMS NIH HHS

• virus-host interactions
• translation

• Antiviral Agents/pharmacology
• Humans
• Adenosine/analogs & derivatives
• Adenosine/metabolism
• SARS-CoV-2/drug effects
• SARS-CoV-2/genetics
• SARS-CoV-2/metabolism
• Protein Biosynthesis/drug effects
• COVID-19 Drug Treatment
• Peptide Elongation Factor 1/metabolism
• Peptide Elongation Factor 1/antagonists & inhibitors
• Internal Ribosome Entry Sites/drug effects
• RNA Caps/metabolism
• RNA Caps/genetics
• Peptides, Cyclic/pharmacology
• COVID-19/virology
• Animals
• RNA-Binding Proteins/metabolism
• HEK293 Cells
• Depsipeptides

• NI-U is supported by the Spanish Ministry of Science and Innovation (grants PID2020-117145RB-I00, PID2023-147498OB-I00 and 10.13039/501100011033, Spain), EU HORIZON-HLTH-2021CORONA-01 (grant 101046118, European Union) and by institutional funding of Pharma Mar, Grifols, HIPRA, and Amassence. EM-M is supported by the Spanish Ministry of Science and Innovation (grant PRE2021-099271). EF is supported by JDC2023-050389-I funded by MCIU/AEI/10.13039/501100011033 and FSE+.

• Caenorhabditis elegans
• Cell atlas
• Eggs during embryonation
• Essential gene
• Eukaryotic elongation factor
• Haemonchus contortus
• Interaction network
• Intervention target candidate
• Protein biosynthesis
• Single cell/nucleus RNA-sequencing

• C. elegans
• PUF RNA binding protein
• PUF partnerships
• germline stem cells
• sperm/oocyte cell fate decision

• P40 OD010440 NIH HHS
• R01 GM050942 NIGMS NIH HHS
• R01 GM134119 NIGMS NIH HHS

• Argonaute
• CENP-A
• Centromere
• Chromosome segregation
• HCP-3
• Kinetochore
• RNA interference

• Animals
• Caenorhabditis elegans/metabolism
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans Proteins/metabolism
• Caenorhabditis elegans Proteins/genetics
• Centromere Protein A/metabolism
• Centromere Protein A/genetics
• Kinetochores/metabolism
• Chromosome Segregation
• Centromere/metabolism
• Argonaute Proteins/metabolism
• Argonaute Proteins/genetics
• Mitosis
• Chromosomal Proteins, Non-Histone/metabolism
• Chromosomal Proteins, Non-Histone/genetics
• RNA Interference
• Histones/metabolism
• Histones/genetics
• Chromatin/metabolism
• RNA-Dependent RNA Polymerase

• 2021YFA0909300 National Key Research and Development Program of China
• 17126717 Research Council of Hong Kong
• University of Hong Kong

• C. elegans germline
• GLD-1
• GLP-1/Notch signaling
• PUF-8
• RNA-binding proteins
• tumorigenesis

• R15 AG060373 NIA NIH HHS
• 217045 Lung Cancer Initiative
• AG060373-01 NIH HHS
• IOS 2132286 NSF

• COP9 signalosome
• COPS5
• CSN-2
• CSN-6
• PUM1
• germline
• oocyte development

• Animals
• Caenorhabditis elegans/cytology
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans/metabolism
• Caenorhabditis elegans Proteins/metabolism
• Caenorhabditis elegans Proteins/genetics
• COP9 Signalosome Complex/metabolism
• COP9 Signalosome Complex/genetics
• Germ Cells/metabolism
• Oogenesis/genetics
• Protein Stability
• RNA-Binding Proteins/metabolism
• RNA-Binding Proteins/genetics
• Stem Cells/metabolism
• Stem Cells/cytology

• R01GM109053 NIH HHS
• P40 OD010440 NIH HHS
• R01 GM109053 NIGMS NIH HHS
• S10 OD021806 NIH HHS
• P20 GM103546 NIGMS NIH HHS
• P20 GM103474 NIGMS NIH HHS
• NIH
• Toelle-Bekken Family Memorial Fund

• C. elegans
• FBF-2
• FBF-binding elements
• PUF/PUM partner proteins
• PUF/PUM-RNA-binding protein
• RNA binding landscape
• eCLIP
• germline stem cells
• gld-1 RNA
• sperm/oocyte fate decision

• Male
• Animals
• Caenorhabditis elegans/metabolism
• Caenorhabditis elegans Proteins/metabolism
• Semen/metabolism
• RNA/metabolism
• RNA-Binding Proteins/metabolism

• P40 OD010440 NIH HHS
• R01 GM050942 NIGMS NIH HHS
• R01 GM134119 NIGMS NIH HHS

• AGO2
• FMRP
• RBP interactome
• RNA-binding protein interactome
• brain interactome

• Animals
• Mice
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Mutation
• Brain/metabolism
• Seizures

• R01 HG012216 NHGRI NIH HHS
• R35 GM128802 NIGMS NIH HHS
• R35 GM128855 NIGMS NIH HHS
• R01 AG071869 NIA NIH HHS
• R01 NS109858 NINDS NIH HHS
• Brain and Behavior Research Foundation (BBRF)
• Columbia University Irving Medical Center
• HHS | NIH | National Human Genome Research Institute (NHGRI)
• HHS | NIH | National Institute of General Medical Sciences (NIGMS)
• HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)

• CNOT complex
• Intrinsically disordered proteins
• Network hub
• RNA repression

• Animals
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans/metabolism
• Caenorhabditis elegans Proteins/genetics
• Caenorhabditis elegans Proteins/metabolism
• Germ Cells/metabolism
• RNA/metabolism
• Stem Cells/metabolism

• P40 OD010440 NIH HHS
• R01 GM050942 NIGMS NIH HHS
• R01 GM134119 NIGMS NIH HHS
• National Science Foundation
• National Institutes of Health
• University of Wisconsin Foundation

• intrinsically disordered proteins
• rna repression
• cnot complex
• network hub

• R01 GM050942 NIGMS NIH HHS
• R01 GM069454 NIGMS NIH HHS
• R01 GM134119 NIGMS NIH HHS

• Cancer
• Proliferation
• Pumilio 1
• Pumilio 2
• RNA-binding protein

• RNA, Messenger
• MicroRNAs/genetics

• BB/K009303/1 Biotechnology and Biological Sciences Research Council
• P30 CA016058 NCI NIH HHS
• R01 CA251753 NCI NIH HHS
• National Cancer Institute
• American Cancer Society
• BBSRC
• Royal Society Wolfson
• CNPq Science
• NCI

Eukaryotic organisms have a posttranscriptional/translational regulation system for the control of translational efficiency. RNA binding proteins (RBPs) have been known to control target genes. One type of protein, Pumilio (Pum)/Puf family RNA binding proteins, show a specific binding of 3′ untranslational region (3′ UTR) of target mRNA and function as a post-transcriptional/translational regulator in eukaryotic cells. Plant Pum protein is involved in development and biotic/abiotic stresses. Interestingly, Arabidopsis Pum can control target genes in a sequence-specific manner and rRNA processing in a sequence-nonspecific manner. As shown in in silico Pum gene expression analysis, Arabidopsis and rice Pum genes are responsive to biotic/abiotic stresses. Plant Pum can commonly contribute to host gene regulation at the post-transcriptional/translational step, as can mammalian Pum. However, the function of plant Pum proteins is not yet fully known. In this review, we briefly summarize the function of plant Pum in defense, development, and environmental responses via recent research and bioinformatics data.

• Pumilio
• RNA binding protein
• RNA biomolecules
• translational modification

The regulation of mRNA translation, both globally and at the level of individual transcripts, plays a central role in the development and function of germ cells across species. Genetic studies using flies, worms, zebrafish and mice have highlighted the importance of specific RNA binding proteins in driving various aspects of germ cell formation and function. Many of these mRNA binding proteins, including Pumilio, Nanos, Vasa and Dazl have been conserved through evolution, specifically mark germ cells, and carry out similar functions across species. These proteins typically influence mRNA translation by binding to specific elements within the 3′ untranslated region (UTR) of target messages. Emerging evidence indicates that the global regulation of mRNA translation also plays an important role in germ cell development. For example, ribosome biogenesis is often regulated in a stage specific manner during gametogenesis. Moreover, oocytes need to produce and store a sufficient number of ribosomes to support the development of the early embryo until the initiation of zygotic transcription. Accumulating evidence indicates that disruption of mRNA translation regulatory mechanisms likely contributes to infertility and reproductive aging in humans. These findings highlight the importance of gaining further insights into the mechanisms that control mRNA translation within germ cells. Future work in this area will likely have important impacts beyond germ cell biology.

• aging
• development
• germline
• mRNA translation
• ribosome
• ribosome biogenesis

CSR-1 is an essential Argonaute protein that binds to a subclass of 22G-RNAs targeting most germline-expressed genes. Here we show that the two isoforms of CSR-1 have distinct expression patterns; CSR-1B is ubiquitously expressed throughout the germline and during all stages of development while CSR-1A expression is restricted to germ cells undergoing spermatogenesis. Furthermore, CSR-1A associates preferentially with 22G-RNAs mapping to spermatogenesis-specific genes whereas CSR-1B-bound small RNAs map predominantly to oogenesis-specific genes. Interestingly, the exon unique to CSR-1A contains multiple dimethylarginine modifications, which are necessary for the preferential binding of CSR-1A to spermatogenesis-specific 22G-RNAs. Thus, we have discovered a regulatory mechanism for C. elegans Argonaute proteins that allows for specificity of small RNA binding between similar Argonaute proteins with overlapping temporal and spatial localization.

The Argonaute protein CSR-1 is essential for fertility and viability in C. elegans. Here the authors show that CSR-1A isoform associates preferentially with small RNAs mapping to spermatogenesis-specific genes while CSR-1B isoform binds small RNAs mapping to oogenesis-specific genes. Arginine methylation of CSR-1A promotes small RNA-binding specificity.

• Animals
• Humans
• Mice
• 3' Untranslated Regions/genetics
• Argonaute Proteins/genetics
• Argonaute Proteins/metabolism
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Melanoma/genetics
• Melanoma/pathology
• Melanoma/metabolism
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• MicroRNAs/genetics
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• RNA-Induced Silencing Complex/genetics
• RNA-Induced Silencing Complex/metabolism
• DNA-Binding Proteins

• BRAF
• Cancer
• MYC
• Mutation
• PD-L1
• Polyadenylation
• RNA-binding protein
• Splicing
• Structural variation
• TP53
• UTR
• mRNA
• microRNA

• autism
• epilepsy
• intellectual disabilities
• local protein synthesis
• synaptic dysfunction
• synaptic plasticity

• RNA binding proteins (RBPs)
• computational modeling
• free energy calculations
• gene transcription
• molecular dynamics simulation

Translational regulation of mRNAs is critically important for proper gene expression in germ cells, gametes, and embryos. The ability of the nucleus to control gene expression in these systems may be limited due to spatial or temporal constraints, as well as the breadth of gene products they express to prepare for the rapid animal development that follows. During development germ granules are hubs of post-transcriptional regulation of mRNAs. They assemble and remodel messenger ribonucleoprotein (mRNP) complexes for translational repression or activation. Recently, mRNPs have been appreciated as discrete regulatory units, whose function is dictated by the many positive and negative acting factors within the complex. Repressed mRNPs must be activated for translation on ribosomes to introduce novel proteins into germ cells. The binding of eIF4E to interacting proteins (4EIPs) that sequester it represents a node that controls many aspects of mRNP fate including localization, stability, poly(A) elongation, deadenylation, and translational activation/repression. Furthermore, plants and animals have evolved to express multiple functionally distinct eIF4E and 4EIP variants within germ cells, giving rise to different modes of translational regulation.

• 4EIPs
• RBPs
• deadenylation
• eIF4E
• germ granules
• mRNA decay
• polyadenylation
• translational control

• mTOR
• ribosome density index
• ribosome processivity
• ribosome profiling
• translation elongation

Stem cell development depends on post-transcriptional regulation mediated by RNA-binding proteins (RBPs) (Zhang et al., 1997; Forbes and Lehmann, 1998; Okano et al., 2005; Ratti et al., 2006; Kwon et al., 2013). Pumilio and FBF (PUF) family RBPs are highly conserved post-transcriptional regulators that are critical for stem cell maintenance (Wickens et al., 2002; Quenault et al., 2011). The RNA-binding domains of PUF proteins recognize a family of related sequence motifs in the target mRNAs, yet individual PUF proteins have clearly distinct biological functions (Lu et al., 2009; Wang et al., 2018). The C. elegans germline is a simple and powerful model system for analyzing regulation of stem cell development. Studies in C. elegans uncovered specific physiological roles for PUFs expressed in the germline stem cells ranging from control of proliferation and differentiation to regulation of the sperm/oocyte decision. Importantly, recent studies started to illuminate the mechanisms behind PUF functional divergence. This review summarizes the many roles of PUF-8, FBF-1, and FBF-2 in germline stem and progenitor cells (SPCs) and discusses the factors accounting for their distinct biological functions. PUF proteins are conserved in evolution, and insights into PUF-mediated regulation provided by the C. elegans model system are likely relevant for other organisms.

• C. elegans
• RNA regulation
• germline
• pumilio and fem-3-binding factor
• stem cells

Activity-dependent protein synthesis plays an important role during neuronal development by fine-tuning the formation and function of neuronal circuits. Recent studies have shown that miRNAs are integral to this regulation because of their ability to control protein synthesis in a rapid, specific and potentially reversible manner. miRNA mediated regulation is a multistep process that involves inhibition of translation before degradation of targeted mRNA, which provides the possibility to store and reverse the inhibition at multiple stages. This flexibility is primarily thought to be derived from the composition of miRNA induced silencing complex (miRISC). AGO2 is likely the only obligatory component of miRISC, while multiple RBPs are shown to be associated with this core miRISC to form diverse miRISC complexes. The formation of these heterogeneous miRISC complexes is intricately regulated by various extracellular signals and cell-specific contexts. In this review, we discuss the composition of miRISC and its functions during neuronal development. Neurodevelopment is guided by both internal programs and external cues. Neuronal activity and external signals play an important role in the formation and refining of the neuronal network. miRISC composition and diversity have a critical role at distinct stages of neurodevelopment. Even though there is a good amount of literature available on the role of miRNAs mediated regulation of neuronal development, surprisingly the role of miRISC composition and its functional dynamics in neuronal development is not much discussed. In this article, we review the available literature on the heterogeneity of the neuronal miRISC composition and how this may influence translation regulation in the context of neuronal development.

• miRISC
• miRNA
• neuronal activity
• neuronal development
• translation regulation

PUMILIO/FBF (PUF) proteins have a conserved function in stem cell regulation. Caenorhabditis elegans PUF-8 protein inhibits the translation of target mRNAs by interacting with PUF binding element (PBE) in the 3′ untranslated region (3′ UTR). In this work, an in silico analysis has identified gld-2 [a poly(A) polymerase] as a putative PUF-8 target. Biochemical and reporter analyses showed that PUF-8 specifically binds to a PBE in gld-2 3′ UTR and represses a GFP reporter gene carrying gld-2 3′ UTR in the C. elegans mitotic germ cells. GLD-2 enhances meiotic entry at least in part by activating GLD-1 (a KH motif-containing RNA-binding protein). Our genetic analyses also demonstrated that heterozygous gld-2(+/−) gld-1(+/−) genes in the absence of PUF-8 are competent for meiotic entry (early differentiation), but haplo-insufficient for the meiotic division (terminal differentiation) of spermatocytes. Indeed, the arrested spermatocytes return to mitotic cells via dedifferentiation, which results in germline tumors. Since these regulators are broadly conserved, we thus suggest that similar molecular mechanisms may control differentiation, dedifferentiation, and tumorigenesis in other organisms, including humans.

• C. elegans
• GLD-2
• PUF-8
• dedifferentiation
• differentiation

• cleavage and polyadenylation factors in plants
• increase gene expression in plants
• molecular biotechnology
• plant 3’ regulatory regions
• plant cis-regulatory elements

• CRISPR-Cas
• Pentatricopeptide repeat protein
• Pumilio/fem-3 binding factor
• RNA binding protein

• Cell Nucleus/metabolism
• Cytoplasm/metabolism
• Plant Proteins/genetics
• Plant Proteins/metabolism
• Plants/genetics
• Plants/metabolism
• Plastids/metabolism
• RNA/genetics
• RNA/metabolism
• RNA Editing
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism

• 3′UTR
• PUF protein
• RhBRC1
• shoot branching
• sucrose metabolism

• 3' Untranslated Regions/genetics
• Arabidopsis/genetics
• Arabidopsis/metabolism
• Arabidopsis Proteins/genetics
• Gene Expression Regulation, Plant/genetics
• Phenotype
• Plant Proteins/genetics
• RNA-Binding Proteins/genetics
• Rosa/genetics
• Rosa/metabolism
• Signal Transduction/genetics
• Sugars/metabolism
• Transcription Factors/genetics

Response gene to complement-32 (RGC-32) activates cyclin-dependent kinase 1, regulates the cell cycle and is deregulated in many human tumours. We previously showed that RGC-32 expression is upregulated by the cancer-associated Epstein-Barr virus (EBV) in latently infected B cells through the relief of translational repression. We now show that EBV infection of naïve primary B cells also induces RGC-32 protein translation. In EBV-immortalised cell lines, we found that RGC-32 depletion resulted in cell death, indicating a key role in B cell survival. Studying RGC-32 translational control in EBV-infected cells, we found that the RGC-32 3′untranslated region (3′UTR) mediates translational repression. Repression was dependent on a single Pumilio binding element (PBE) adjacent to the polyadenylation signal. Mutation of this PBE did not affect mRNA cleavage, but resulted in increased polyA tail length. Consistent with Pumilio-dependent recruitment of deadenylases, we found that depletion of Pumilio in EBV-infected cells increased RGC-32 protein expression and polyA tail length. The extent of Pumilio binding to the endogenous RGC-32 mRNA in EBV-infected cell lines also correlated with RGC-32 protein expression. Our data demonstrate the importance of RGC-32 for the survival of EBV-immortalised B cells and identify Pumilio as a key regulator of RGC-32 translation.

Behavior and higher cognition rely on the transfer of information between neurons through specialized contact sites termed synapses. Plasticity of neuronal circuits, a prerequisite to respond to environmental changes, is intrinsically coupled with the nerve cell’s ability to form, structurally modulate or remove synapses. Consequently, the synaptic proteome undergoes dynamic alteration on demand in a spatiotemporally restricted manner. Therefore, proper protein localization at synapses is essential for synaptic function. This process is regulated by: (i) protein transport and recruitment; (ii) local protein synthesis; and (iii) synaptic protein degradation. These processes shape the transmission efficiency of excitatory synapses. Whether and how these processes influence synaptic inhibition is, however, widely unknown. Here, we summarize findings on fundamental regulatory processes that can be extrapolated to inhibitory synapses. In particular, we focus on known aspects of posttranscriptional regulation and protein dynamics of the GABA receptor (GABAR). Finally, we propose that local (co)-translational control mechanism might control transmission of inhibitory synapses.

• GABA receptors
• RNA binding
• RNA transport
• RNA-binding proteins
• co-translational folding/assembly
• inhibitory synapse
• local translation
• posttranscriptional gene regulation

• ABA
• APUM9
• PUMILIO/PUF protein
• Plant development and heat tolerance
• RNA-binding protein
• Transposable element

• Adaptation, Physiological
• Arabidopsis/metabolism
• Arabidopsis/physiology
• Arabidopsis Proteins/genetics
• Arabidopsis Proteins/metabolism
• Catalytic Domain
• Conserved Sequence
• DNA Transposable Elements/genetics
• Plant Development
• Plant Dormancy
• Protein Binding
• Protein Domains
• RNA Stability
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Seeds/metabolism
• Stress, Physiological

• ConnecTalent grant from the Pays de la Loire

• AGO
• GW182
• miRISC
• miRNA

• Arabidopsis/genetics
• Arabidopsis/metabolism
• Arabidopsis Proteins/genetics
• Arabidopsis Proteins/metabolism
• Arabidopsis Proteins/physiology
• Argonaute Proteins/genetics
• Argonaute Proteins/metabolism
• Argonaute Proteins/physiology
• DNA Repair
• Gene Silencing
• MicroRNAs/genetics
• MicroRNAs/metabolism
• MicroRNAs/physiology
• Models, Molecular
• RNA Interference

• Narodowe Centrum Nauki (Polish National Science Centre)

PUF (PUmilio/FBF) RNA-binding proteins recognize distinct elements. In C. elegans, PUF-8 binds to an 8-nt motif and restricts proliferation in the germline. Conversely, FBF-2 recognizes a 9-nt element and promotes mitosis. To understand how motif divergence relates to biological function, we first determined a crystal structure of PUF-8. Comparison of this structure to that of FBF-2 revealed a major difference in a central repeat. We devised a modified yeast 3-hybrid screen to identify mutations that confer recognition of an 8-nt element to FBF-2. We identified several such mutants and validated structurally and biochemically their binding to 8-nt RNA elements. Using genome engineering, we generated a mutant animal with a substitution in FBF-2 that confers preferential binding to the PUF-8 element. The mutant largely rescued overproliferation in animals that spontaneously generate tumors in the absence of puf-8. This work highlights the critical role of motif length in the specification of biological function.

• C. elegans
• FBF
• Motif
• PUF
• RNA-binding
• developmental biology
• elegans
• molecular biophysics
• pumilio
• structural biology

• Ubr5
• chronic inflammation pain
• circRNA-Filipi1l
• miRNA-1224
• spinal

• FBF
• germline stem cell
• iCLIP
• oocyte
• sperm

• Animals
• Binding Sites
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans/growth & development
• Caenorhabditis elegans Proteins/genetics
• Female
• Male
• Oocytes/growth & development
• Oocytes/metabolism
• Oogenesis/genetics
• Phylogeny
• Protein Binding/genetics
• RNA-Binding Proteins/genetics
• Sex Determination Processes/genetics
• Spermatogenesis/genetics
• Spermatozoa/growth & development
• Spermatozoa/metabolism
• Stem Cells/metabolism

• R01 GM050942 NIGMS NIH HHS
• T32 GM008349 NIGMS NIH HHS
• R01 GM069454 NIGMS NIH HHS
• Howard Hughes Medical Institute
• T32 GM008692 NIGMS NIH HHS

• Argonaute
• MicroRNA
• Molecular dynamics
• RISC
• RISC-SNPs
• Tertiary structure modeling
• miRNA target recognition

• Argonaute Proteins/chemistry
• Binding Sites
• Computational Biology/methods
• Gene Expression Regulation
• Humans
• MicroRNAs/chemistry
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Protein Structure, Tertiary
• RNA, Messenger/chemistry
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA-Induced Silencing Complex/chemistry
• RNA-Induced Silencing Complex/metabolism
• Software

• C. elegans
• PUF protein
• RNA
• RNA-binding protein
• X-ray crystallography
• developmental biology
• molecular biophysics
• structural biology

• Animals
• Gene Expression Regulation/genetics
• Gene Regulatory Networks/genetics
• Humans
• Mammals/genetics
• RNA Stability/genetics
• RNA, Messenger/genetics
• RNA, Untranslated/genetics
• RNA-Binding Proteins/genetics

• R01 GM105707 NIGMS NIH HHS
• Z01 ES050165-11 Intramural NIH HHS
• ZIA ES050165-21 Intramural NIH HHS

• Eukaryota/genetics
• Gene Expression Regulation
• Models, Genetic
• Protein Biosynthesis
• RNA Stability
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

• R01 AI123136 NIAID NIH HHS
• R21 AI130497 NIAID NIH HHS

Endogenous RNAi (endoRNAi) is a conserved mechanism for fine-tuning gene expression. In the nematode Caenorhabditis elegans, several endoRNAi pathways are required for the successful development of reproductive cells. The CSR-1 endoRNAi pathway promotes germ cell development, primarily by facilitating the expression of germline genes. In this study, we report a novel function for the CSR-1 pathway in preventing premature activation of embryonic transcription in the developing oocytes, which is accompanied by a general Pol II activation. This CSR-1 function requires its RNase activity, suggesting that, by controlling the levels of maternal mRNAs, CSR-1-dependent endoRNAi contributes to an orderly reprogramming of transcription during the oocyte-to-embryo transition.

During the oocyte-to-embryo transition, the control of development is transferred from the mother to the embryo. A key event during this transition is the transcriptional activation of the embryonic genome, which is tightly controlled. Here, by using the nematode C. elegans, we uncover a role for endogenous RNA interference in this process. We demonstrate that a specific endoRNAi pathway, employing the Argonaute protein CSR-1, functions as a break on gene-specific, and potentially global, activation of embryonic transcription in the developing oocytes. Our findings reveal a new layer of control over the transcriptional reprogramming during the oocyte-to-embryo transition, raising questions about its potential conservation in mammalian development.

• Animals
• Animals, Genetically Modified
• Caenorhabditis elegans/embryology
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans Proteins/genetics
• Caenorhabditis elegans Proteins/metabolism
• Embryo, Nonmammalian
• Female
• Gene Expression Regulation, Developmental
• Mutation
• Oocytes/physiology
• RNA Interference
• RNA Polymerase II/genetics
• RNA Polymerase II/metabolism
• Transcription Factors/genetics

• Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• European Molecular Biology Organization
• Narodowe Centrum Nauki

Post-transcriptional regulation of gene expression plays a crucial role in many processes. In cells, it is mediated by diverse RNA-binding proteins. These proteins can influence mRNA stability, translation, and localization. The PUF protein family (Pumilio and FBF) is composed of RNA-binding proteins highly conserved among most eukaryotic organisms. Previous investigations indicated that they could be involved in many processes by binding corresponding motifs in the 3′UTR or by interacting with other proteins. To date, most of the investigations on PUF proteins have been focused on Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae, while only a few have been conducted on Arabidopsis thaliana. The present article provides an overview of the PUF protein family. It addresses their RNA-binding motifs, biological functions, and post-transcriptional control mechanisms in Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, and Arabidopsis thaliana. These items of knowledge open onto new investigations into the relevance of PUF proteins in specific plant developmental processes.

• PUF protein
• RNA-binding motifs
• plant
• post-transcriptional
• regulation

• Amino Acid Motifs
• Animals
• Arabidopsis/genetics
• Arabidopsis/metabolism
• Arabidopsis Proteins/genetics
• Arabidopsis Proteins/metabolism
• Drosophila
• Drosophila Proteins/genetics
• Drosophila Proteins/metabolism
• Humans
• Multigene Family
• RNA/metabolism
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Saccharomyces cerevisiae/genetics
• Saccharomyces cerevisiae/metabolism
• Saccharomyces cerevisiae Proteins/genetics
• Saccharomyces cerevisiae Proteins/metabolism

Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3′-untranslated regions (UTRs) of mRNAs. mRNA 3′-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay. Each RNA binding protein that binds to these cis-acting elements regulates mRNA translation via various mechanisms targeting the mRNA cap structure, the eukaryotic initiation factor 4E (eIF4E)-eIF4G complex, ribosomes, and the poly (A) tail. We also discuss translation-mediated regulation of mRNA fate.