• deadenylation
• mRNA degradation
• poly(A)
• ribosomal protein mRNAs
• starfish
• uridylation

• Animals
• Starfish/genetics
• Starfish/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Oocytes/metabolism
• Ribosomal Proteins/genetics
• Ribosomal Proteins/metabolism
• RNA Stability
• Embryo, Nonmammalian/metabolism
• Cyclin B/metabolism
• Cyclin B/genetics
• Protein Biosynthesis

• JSPS KAKENHI (JP17K07405, 21K06185 to K.C.) : the Cooperative Program provided by the Atmosphere and Ocean Research Institute, University of Tokyo the Takeda Science Foundation

• RNA
• click reaction
• clickable nucleotides
• fluorescent nucleotides
• terminal nucleotidyl transferase

• Fluorescent Dyes/chemistry
• Click Chemistry
• RNA/chemistry
• RNA/metabolism
• Oligonucleotides/chemistry
• Oligonucleotides/metabolism
• Uridine Triphosphate/chemistry
• Uridine Triphosphate/metabolism
• Uridine Triphosphate/analogs & derivatives
• Alkynes/chemistry
• RNA Nucleotidyltransferases/metabolism
• RNA Nucleotidyltransferases/chemistry
• Azides/chemistry
• Nucleotides/chemistry
• Nucleotides/metabolism

• Prime Minister's Research Fellowship
• CRG/2022/000284 SERB

• rna modification
• oogenesis
• spermatogenesis

• Animals
• Female
• Male
• Polyadenylation
• RNA, Messenger/metabolism
• RNA, Messenger/genetics
• Mice
• Mice, Knockout
• Spermatogenesis/genetics
• Gametogenesis/genetics
• Oogenesis/genetics
• Polynucleotide Adenylyltransferase/metabolism
• Polynucleotide Adenylyltransferase/genetics
• Oocytes/metabolism
• Fertility/genetics
• Mice, Inbred C57BL

• 2019/33/B/NZ2/01773 Narodowe Centrum Nauki (National Science Centre)
• UMO-2019/34/H/NZ3/00733 Narodowe Centrum Nauki (National Science Centre)
• 810425 European Commission (EC)

• Artificial expression system
• C3P3
• Poly(A) polymerase
• Polyadenylation
• mRNA

• Animals
• Humans
• Mice
• Polyadenylation
• DNA-Directed RNA Polymerases/genetics
• RNA, Messenger/metabolism
• Polynucleotide Adenylyltransferase/genetics
• Polynucleotide Adenylyltransferase/metabolism
• Poly A/genetics
• Poly A/metabolism

• Cnidaria
• Ctenophora
• cytoplasmic polyadenylation
• evolution
• post-transcriptional regulation

• Animals
• Phylogeny
• Polyadenylation
• Ctenophora/genetics
• Sea Anemones/genetics

• R15 HD082754 NICHD NIH HHS
• The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health
• Paul G. Allen Family Foundation
• National Science Foundation
• National Aeronautics and Space Administration
• National Science Foundation Postdoctoral Research Fellowship in Biology

• Cpeb1b
• Hedgehog signaling
• cytoplasmic polyadenylation
• hematopoietic stem and progenitor cell
• translational control

• rna
• translation

• COVID-19
• Frameshifting, Ribosomal
• HEK293 Cells
• Host-Pathogen Interactions
• Humans
• Nucleic Acid Conformation
• Protein Isoforms
• Proteome
• RNA, Viral/genetics
• RNA-Binding Proteins/metabolism
• Repressor Proteins/metabolism
• SARS-CoV-2/genetics
• SARS-CoV-2/physiology
• Virus Replication

• 948636 EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
• MWK Niedersachsen Grant Nr. 14-76103-184 CORONA-2/20 (to L.C.S.)

The formation of the Bicoid (Bcd) gradient in the early Drosophila is one of the most fascinating observations in biology and serves as a paradigm for gradient formation, yet its mechanism is still not fully understood. Two distinct models were proposed in the past, the SDD and the ARTS model.

We define novel cis- and trans-acting factors that are indispensable for gradient formation. The first one is the poly A tail length of the bcd mRNA where we demonstrate that it changes not only in time, but also in space. We show that posterior bcd mRNAs possess a longer poly tail than anterior ones and this elongation is likely mediated by wispy (wisp), a poly A polymerase. Consequently, modulating the activity of Wisp results in changes of the Bcd gradient, in controlling downstream targets such as the gap and pair-rule genes, and also in influencing the cuticular pattern. Attempts to modulate the Bcd gradient by subjecting the egg to an extra nuclear cycle, i.e. a 15^th nuclear cycle by means of the maternal haploid (mh) mutation showed no effect, neither on the appearance of the gradient nor on the control of downstream target. This suggests that the segmental anlagen are determined during the first 14 nuclear cycles. Finally, we identify the Cyclin B (CycB) gene as a trans-acting factor that modulates the movement of Bcd such that Bcd movement is allowed to move through the interior of the egg.

Our analysis demonstrates that Bcd gradient formation is far more complex than previously thought requiring a revision of the models of how the gradient is formed.

• RNA stability
• microRNA
• nucleotidyltransferase
• oncogenic kinase
• protein–protein interaction

Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow. The high frequent mutation of family with sequence similarity 46, member C (FAM46C) is closely related with the occurrence and progression of MM. Recently, FAM46C has been identified as a non‐canonical poly(A) polymerase (PAP) that functions as a tumor suppressor in MM. This study aimed to elucidate the structural features of this novel non‐canonical PAP and how MM‐related mutations affect the structural and biochemical properties of FAM46C, eventually advancing our understandings towards FAM46C mutation‐related MM occurrence.

We purified and crystallized a mammalian FAM46C construct, and solved its structure. Next, we characterized the property of FAM46C as a PAP through a combination of structural analysis, site‐directed mutagenesis and biochemical assays, and by comparison with its homolog FAM46B. Finally, we structurally analyzed MM‐related FAM46C mutations and tested the enzymatic activity of corresponding mutants.

We determined the crystal structure of a mammalian FAM46C protein at 2.35 Å, and confirmed that FAM46C preferentially consumed adenosine triphosphate (ATP) and extended A‐rich RNA substrates. FAM46C showed a weaker PAP activity than its homolog FAM46B, and this difference was largely dependent on the residue variance at particular sites. Of them, residues at positions 77, 290, and 298 of mouse FAM46C were most important for the divergence in enzymatic activity. Among the MM‐associated FAM46C mutants, those residing at the catalytic site (D90G and D90H) or putative RNA‐binding site (I155L, S156F, D182Y, F184L, Y247V, and M270V) showed abolished or compromised PAP activity of FAM46C, while N72A and S248A did not severely affect the PAP activity. FAM46C mutants D90G, D90H, I155L, S156F, F184L, Y247V, and M270V had significantly lower inhibitory effect on apoptosis of RPMI‐8226 cells as compared to wild‐type FAM46C.

FAM46C is a prokaryotic‐like PAP with preference for A‐rich RNA substrates, and showed distinct enzymatic efficiency with its homolog FAM46B. The MM‐related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.

• FAM46C
• PTEN
• apoptosis
• crystal structure
• miRNA
• multiple myeloma
• poly(A) polymerase

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

• TENT5
• TUT4/7
• polyadenylation
• terminal nucleotidyltransferase
• uridylation

• Animals
• Caenorhabditis elegans/enzymology
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans Proteins/genetics
• Mutation
• Nucleotidyltransferases/genetics
• RNA Interference
• RNA Nucleotidyltransferases/genetics
• Saccharomyces cerevisiae/enzymology
• Saccharomyces cerevisiae/genetics
• Saccharomyces cerevisiae Proteins/genetics

• R21 HG011371 NHGRI NIH HHS
• R01 HG003747 NHGRI NIH HHS
• F32 GM103130 NIGMS NIH HHS
• R01 GM050942 NIGMS NIH HHS
• T32 GM008349 NIGMS NIH HHS
• Howard Hughes Medical Institute

• Gap junction
• Meiosis
• Oocyte meiotic maturation
• Oogenesis
• Signaling
• Soma-germline interactions
• Translational regulation

• Animals
• Caenorhabditis elegans
• Embryonic Development/physiology
• Humans
• Meiosis/physiology
• Oocytes/cytology
• Oogenesis/physiology
• Signal Transduction/physiology

• R01 GM057173 NIGMS NIH HHS
• R21 NS095109 NINDS NIH HHS

RNA uridylylation plays a pivotal role in the biogenesis and metabolism of functional RNAs, and regulates cellular gene expression. RNA uridylylation is catalyzed by a subset of proteins from the non-canonical terminal nucleotidyltransferase family. In human, three proteins (TUT1, TUT4, and TUT7) have been shown to exhibit template-independent uridylylation activity at 3′-end of specific RNAs. TUT1 catalyzes oligo-uridylylation of U6 small nuclear (sn) RNA, which catalyzes mRNA splicing. Oligo-uridylylation of U6 snRNA is required for U6 snRNA maturation, U4/U6-di-snRNP formation, and U6 snRNA recycling during mRNA splicing. TUT4 and TUT7 catalyze mono- or oligo-uridylylation of precursor let-7 (pre–let-7). Let-7 RNA is broadly expressed in somatic cells and regulates cellular proliferation and differentiation. Mono-uridylylation of pre–let-7 by TUT4/7 promotes subsequent Dicer processing to up-regulate let-7 biogenesis. Oligo-uridylylation of pre–let-7 by TUT4/7 is dependent on an RNA-binding protein, Lin28. Oligo-uridylylated pre–let-7 is less responsive to processing by Dicer and degraded by an exonuclease DIS3L2. As a result, let-7 expression is repressed. Uridylylation of pre–let-7 depends on the context of the 3′-region of pre–let-7 and cell type. In this review, we focus on the 3′ uridylylation of U6 snRNA and pre-let-7, and describe the current understanding of mechanism of activity and regulation of human TUT1 and TUT4/7, based on their crystal structures that have been recently solved.

• TUT1
• TUT4/7
• TUTase
• U6 snRNA
• biogenesis
• let-7
• splicing
• terminal uridylyltransferase

• RNA degradation
• RNA modification
• RNA processing
• RNA surveillance
• RNA uridylation
• tutase

In eukaryotes, almost all RNA species are processed at their 3′ ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases. In recent years, several terminal nucleotidyl transferases (TENTs) including non-canonical poly(A) polymerases (ncPAPs) and terminal uridyl transferases (TUTases) have been discovered. In contrast to canonical polymerases, TENTs' functions are more diverse; some, especially TUTases, induce RNA decay while others, such as cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. The mammalian genome encodes 11 different TENTs. This review summarizes the current knowledge about the functions and mechanisms of action of these enzymes.

This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.

• RNA metabolism
• RNA stability
• RNA uridylation
• TENT
• TUTase
• non-canonical polyadenylation

• 3′-RACE-seq
• CutA
• NTP specificity
• noncanonical poly(A) polymerase
• nucleotidyltransferase (NTase)

• Amino Acid Sequence
• Aspergillus nidulans/enzymology
• Computational Biology/methods
• Cytidine/chemistry
• Cytidine Triphosphate/chemistry
• Cytidine Triphosphate/metabolism
• Fungal Proteins/chemistry
• Fungal Proteins/metabolism
• Models, Molecular
• Nucleotidyltransferases/chemistry
• Nucleotidyltransferases/metabolism
• Sequence Homology
• Substrate Specificity

• European Research Council

• germline development
• poly(A) metabolism
• poly(A) polymerase
• translational regulation

• Amino Acid Sequence
• Animals
• Animals, Genetically Modified
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans/growth & development
• Caenorhabditis elegans/metabolism
• Caenorhabditis elegans Proteins/genetics
• Caenorhabditis elegans Proteins/metabolism
• Gene Expression Regulation
• Mutation, Missense/genetics
• Poly A/metabolism
• Polyadenylation
• Polynucleotide Adenylyltransferase/genetics
• Polynucleotide Adenylyltransferase/metabolism
• RNA Processing, Post-Transcriptional
• RNA Stability
• RNA, Messenger/metabolism
• Sequence Alignment

• Embryonic asymmetry
• Maternal mRNA
• Regulated translation
• Xenopus

An extended meiotic prophase is a hallmark of oogenesis. Hormonal signaling activates the CDK1/cyclin B kinase to promote oocyte meiotic maturation, which involves nuclear and cytoplasmic events. Nuclear maturation encompasses nuclear envelope breakdown, meiotic spindle assembly, and chromosome segregation. Cytoplasmic maturation involves major changes in oocyte protein translation and cytoplasmic organelles and is poorly understood. In the nematode Caenorhabditis elegans, sperm release the major sperm protein (MSP) hormone to promote oocyte growth and meiotic maturation. Large translational regulatory ribonucleoprotein (RNP) complexes containing the RNA-binding proteins OMA-1, OMA-2, and LIN-41 regulate meiotic maturation downstream of MSP signaling. To understand the control of translation during meiotic maturation, we purified LIN-41-containing RNPs and characterized their protein and RNA components. Protein constituents of LIN-41 RNPs include essential RNA-binding proteins, the GLD-2 cytoplasmic poly(A) polymerase, the CCR4-NOT deadenylase complex, and translation initiation factors. RNA sequencing defined messenger RNAs (mRNAs) associated with both LIN-41 and OMA-1, as well as sets of mRNAs associated with either LIN-41 or OMA-1. Genetic and genomic evidence suggests that GLD-2, which is a component of LIN-41 RNPs, stimulates the efficient translation of many LIN-41-associated transcripts. We analyzed the translational regulation of two transcripts specifically associated with LIN-41 which encode the RNA regulators SPN-4 and MEG-1. We found that LIN-41 represses translation of spn-4 and meg-1, whereas OMA-1 and OMA-2 promote their expression. Upon their synthesis, SPN-4 and MEG-1 assemble into LIN-41 RNPs prior to their functions in the embryo. This study defines a translational repression-to-activation switch as a key element of cytoplasmic maturation.

• RNA-binding proteins
• cytoplasmic polyadenylation
• oocyte meiotic maturation
• ribonucleoprotein particle purification
• translational regulation

• Nucleotidyltransferases
• Posttranscriptional RNA editing
• RNA labeling
• RNA stability
• miRNA maturation

• CPEB1
• WEE1
• cell cycle
• cytoplasmic polyadenylation
• miR-15b
• translational regulation

Uridylation of various cellular RNA species at the 3′ end has been generally linked to RNA degradation. In mammals, uridylated pre‐let‐7 miRNAs and mRNAs are targeted by the 3′ to 5′ exoribonuclease DIS3L2. Mutations in DIS3L2 have been associated with Perlman syndrome and with Wilms tumor susceptibility. Using in vivo cross‐linking and immunoprecipitation (CLIP) method, we discovered the DIS3L2‐dependent cytoplasmic uridylome of human cells. We found a broad spectrum of uridylated RNAs including rRNAs, snRNAs, snoRNAs, tRNAs, vault, 7SL, Y RNAs, mRNAs, lncRNAs, and transcripts from pseudogenes. The unifying features of most of these identified RNAs are aberrant processing and the presence of stable secondary structures. Most importantly, we demonstrate that uridylation mediates DIS3L2 degradation of short RNA polymerase II‐derived RNAs. Our findings establish the role of DIS3L2 and oligouridylation as the cytoplasmic quality control for highly structured ncRNAs.

• DIS3L2
• RNA surveillance
• TSSa
• ncRNAs
• uridylation

The testis-specific cytoplasmic poly(A) polymerase PAPOLB/TPAP is essential for spermatogenesis. Although this enzyme is responsible for poly(A) tail extension of a subset of mRNAs in round spermatids, the stability and translational efficiency of these mRNAs are unaffected by the absence of PAPOLB. To clarify the functional importance of this enzyme’s adenylation activity, we produced PAPOLB-null mice expressing a polyadenylation-defective PAPOLB mutant (PAPOLB^D114A), in which the catalytic Asp at residue 114 was mutated to Ala. Introducing PAPOLB^D114A failed to rescue PAPOLB-null phenotypes, such as reduced expression of haploid-specific mRNAs, spermiogenesis arrest, and male infertility. These results suggest that PAPOLB regulates spermatogenesis through its adenylation activity.

• C. elegans
• cytoplasmic polyadenylation
• germline development
• nucleotidyl-transferase
• translational regulation

• Animals
• Caenorhabditis elegans/enzymology
• Caenorhabditis elegans Proteins/chemistry
• Caenorhabditis elegans Proteins/physiology
• Crystallography, X-Ray
• Polynucleotide Adenylyltransferase/chemistry
• Polynucleotide Adenylyltransferase/metabolism
• Polynucleotide Adenylyltransferase/physiology
• Protein Conformation
• RNA-Binding Proteins/chemistry
• RNA-Binding Proteins/physiology
• Ribonucleoproteins/chemistry
• Ribonucleoproteins/physiology

• adenylation
• miRNA
• miRNA maturation
• nucleotidyltransferase
• uridylation

• Biological Evolution
• HEK293 Cells
• Humans
• Mutagenesis, Site-Directed
• Nucleotides/metabolism
• Polynucleotide Adenylyltransferase
• Recombinant Proteins/metabolism
• Substrate Specificity
• mRNA Cleavage and Polyadenylation Factors/genetics
• mRNA Cleavage and Polyadenylation Factors/metabolism

Here, Lim et al. report a new version of TAIL-seq (mRNA TAIL-seq [mTAIL-seq]) with enhanced sequencing depth for mRNAs (by ∼1000-fold compared with the previous version). Using their new methodology, the authors investigated mRNA tailing in Drosophila oocytes and embryos and demonstrated a relationship between poly(A) tail length and translational efficiency during egg activation.

Eukaryotic mRNAs are subject to multiple types of tailing that critically influence mRNA stability and translatability. To investigate RNA tails at the genomic scale, we previously developed TAIL-seq, but its low sensitivity precluded its application to biological materials of minute quantity. In this study, we report a new version of TAIL-seq (mRNA TAIL-seq [mTAIL-seq]) with enhanced sequencing depth for mRNAs (by ∼1000-fold compared with the previous version). The improved method allows us to investigate the regulation of poly(A) tails in Drosophila oocytes and embryos. We found that maternal mRNAs are polyadenylated mainly during late oogenesis, prior to fertilization, and that further modulation occurs upon egg activation. Wispy, a noncanonical poly(A) polymerase, adenylates the vast majority of maternal mRNAs, with a few intriguing exceptions such as ribosomal protein transcripts. By comparing mTAIL-seq data with ribosome profiling data, we found a strong coupling between poly(A) tail length and translational efficiency during egg activation. Our data suggest that regulation of poly(A) tails in oocytes shapes the translatomic landscape of embryos, thereby directing the onset of animal development. By virtue of the high sensitivity, low cost, technical robustness, and broad accessibility, mTAIL-seq will be a potent tool to improve our understanding of mRNA tailing in diverse biological systems.

• Drosophila
• TAIL-seq
• cytoplasmic polyadenylation
• egg activation
• oogenesis
• poly(A) tail

• mRNA uridylation
• oligo(U)
• oocyte
• poly(A)
• polyadenylation
• starfish

• 3' Untranslated Regions
• Animals
• Cyclin B/genetics
• Oocytes/cytology
• Oocytes/metabolism
• Poly A/genetics
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Starfish
• Uridine/metabolism

FAM46 proteins, encoded in all known animal genomes, belong to the nucleotidyltransferase (NTase) fold superfamily. All four human FAM46 paralogs (FAM46A, FAM46B, FAM46C, FAM46D) are thought to be involved in several diseases, with FAM46C reported as a causal driver of multiple myeloma; however, their exact functions remain unknown. By using a combination of various bioinformatics analyses (e.g. domain architecture, cellular localization) and exhaustive literature and database searches (e.g. expression profiles, protein interactors), we classified FAM46 proteins as active non-canonical poly(A) polymerases, which modify cytosolic and/or nuclear RNA 3′ ends. These proteins may thus regulate gene expression and probably play a critical role during cell differentiation. A detailed analysis of sequence and structure diversity of known NTases possessing PAP/OAS1 SBD domain, combined with state-of-the-art comparative modelling, allowed us to identify potential active site residues responsible for catalysis and substrate binding. We also explored the role of single point mutations found in human cancers and propose that FAM46 genes may be involved in the development of other major malignancies including lung, colorectal, hepatocellular, head and neck, urothelial, endometrial and renal papillary carcinomas and melanoma. Identification of these novel enzymes taking part in RNA metabolism in eukaryotes may guide their further functional studies.

• CRISPR-Cas9
• Germ cell
• Germ line
• Germ plasm
• MS2
• Maternal effect
• Maternal specification
• Morpholino
• RNAscope
• Zebrafish

• C. elegans
• RNA regulation
• germ cells
• poly(A) polymerases
• transit-amplifying cells

• 4E-T
• CAF1
• CCR4–NOT
• NOT1
• Xp54
• translation

• Animals
• Humans
• Immunoprecipitation
• Mass Spectrometry
• Nucleocytoplasmic Transport Proteins/metabolism
• Protein Biosynthesis/physiology
• Transcription Factors/metabolism
• Transcription Factors/physiology
• Xenopus

• GM50942 NIGMS NIH HHS
• R01 GM050942 NIGMS NIH HHS
• R37 GM031892 NIGMS NIH HHS
• R01 GM080148 NIGMS NIH HHS
• GM31892 NIGMS NIH HHS
• GM80148 NIGMS NIH HHS
• R01 GM031892 NIGMS NIH HHS

• cytoplasmic poly(A)-polymerase
• cytoplasmic polyadenylation
• germ-line maturation
• noncanonical poly(A)-polymerase
• posttranscriptional regulation

Post-transcriptional gene regulation mechanisms decide on cellular mRNA activities. Essential gatekeepers of post-transcriptional mRNA regulation are broadly conserved mRNA-modifying enzymes, such as cytoplasmic poly(A) polymerases (cytoPAPs). Although these non-canonical nucleotidyltransferases efficiently elongate mRNA poly(A) tails in artificial tethering assays, we still know little about their global impact on poly(A) metabolism and their individual molecular roles in promoting protein production in organisms. Here, we use the animal model Caenorhabditis elegans to investigate the global mechanisms of two germline-enriched cytoPAPs, GLD-2 and GLD-4, by combining polysome profiling with RNA sequencing. Our analyses suggest that GLD-2 activity mediates mRNA stability of many translationally repressed mRNAs. This correlates with a general shortening of long poly(A) tails in gld-2-compromised animals, suggesting that most if not all targets are stabilized via robust GLD-2-mediated polyadenylation. By contrast, only mild polyadenylation defects are found in gld-4-compromised animals and few mRNAs change in abundance. Interestingly, we detect a reduced number of polysomes in gld-4 mutants and GLD-4 protein co-sediments with polysomes, which together suggest that GLD-4 might stimulate or maintain translation directly. Our combined data show that distinct cytoPAPs employ different RNA-regulatory mechanisms to promote gene expression, offering new insights into translational activation of mRNAs.

• 3′-end processing
• CKI
• Canonical PAP
• Oxidative stress
• PAP isoforms
• PAPα
• PI4,5P(2)
• PIPKIα
• Poly(A) polymerase (PAP)
• Polyadenylation
• Star-PAP
• Uridylation

• Animals
• Base Sequence
• Binding Sites
• Consensus Sequence
• Gene Expression Regulation
• Humans
• Nucleotidyltransferases
• Polyadenylation
• Polynucleotide Adenylyltransferase/physiology
• Protein Binding
• Protein Isoforms/physiology
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

• Wellcome Trust
• IA/I/1/505008 Wellcome Trust

• Cell Line
• Down-Regulation
• Hepatitis B virus/metabolism
• Hepatitis B virus/physiology
• Hepatocytes/metabolism
• Hepatocytes/virology
• Humans
• MicroRNAs/genetics
• Polynucleotide Adenylyltransferase
• Trans-Activators/metabolism
• Viral Regulatory and Accessory Proteins
• mRNA Cleavage and Polyadenylation Factors/genetics

The messenger RNA 3’-untranslated region (3’UTR) plays an important role in regulation of gene expression on the posttranscriptional level. The 3’UTR controls gene expression via orchestrated interaction between the structural components of mRNAs (cis-element) and the specific trans-acting factors (RNA binding proteins and non-coding RNAs). The crosstalk of these factors is based on the binding sequences and/or direct protein-protein interaction, or just functional interaction. Much new evidence that has accumulated supports the idea that several RNA binding factors can bind to common mRNA targets: to the non-overlapping binding sites or to common sites in a competitive fashion. Various factors capable of binding to the same RNA can cooperate or be antagonistic in their actions. The outcome of the collective function of all factors bound to the same mRNA 3’UTR depends on many circumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3’UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological conditions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these alterations and their impact on 3’UTR-directed posttranscriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer diagnostics and therapy based on 3’UTR binding factors and approaches to improve them.

• Translational control
• 3’-untranslated region
• MicroRNAs
• RNA binding proteins
• Cancer

• Cytoplasmic polyadenylation
• Egg activation
• Egg-to-embryo transition
• GLD2 family poly(A) polymerase
• Oocyte maturation

• Enzyme Mutation
• Molecular Biology
• Protein-Nucleic Acid Interaction
• RNA Uridylation
• RNA-binding Protein
• TUT7
• Terminal Uridylyl Transferase
• Translation Control
• Xenopus
• ZCCHC6