Alternative polyadenylation of mrna precursors

KEY POINTS * Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates distinct 3′ ends in transcripts made by RNA polymerase II. * APA is tissue specific

and globally regulated in various conditions, such as cell proliferation and differentiation, and in response to extracellular cues. * APA occurring in 3′ untranslated regions (3′ UTRs)

leads to the production of mRNA isoforms with different metabolisms and can also affect protein localization. * APA occurring in the region upstream of the 3′ UTR is often coupled with

splicing and can lead to the production of distinct protein isoforms. It can also function by repressing gene expression. * APA is regulated by several known mechanisms, including regulation

of the levels of core RNA-processing factors and other RNA-binding proteins, as well as by splicing and transcriptional dynamics. ABSTRACT Alternative polyadenylation (APA) is an

RNA-processing mechanism that generates distinct 3′ termini on mRNAs and other RNA polymerase II transcripts. It is widespread across all eukaryotic species and is recognized as a major

mechanism of gene regulation. APA exhibits tissue specificity and is important for cell proliferation and differentiation. In this Review, we discuss the roles of APA in diverse cellular

processes, including mRNA metabolism, protein diversification and protein localization, and more generally in gene regulation. We also discuss the molecular mechanisms underlying APA, such

as variation in the concentration of core processing factors and RNA-binding proteins, as well as transcription-based regulation. Access through your institution Buy or subscribe This is a

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POLYADENYLATION BY SEQUENTIAL ACTIVATION OF DISTAL AND PROXIMAL POLYA SITES Article 10 January 2022 CONTEXT-SPECIFIC REGULATION AND FUNCTION OF MRNA ALTERNATIVE POLYADENYLATION Article 07

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Scholar  Download references ACKNOWLEDGEMENTS The authors thank members of their laboratories for helpful discussions, and I. Boluck for assistance with manuscript preparation. Work in the

authors' laboratories was funded by grants GM84089 (B.T.), and GM28983 and GM118136 (J.L.M.) from the US National Institutes of Health. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, 07103, New Jersey, USA Bin Tian * Department of Biological Sciences,

Columbia University, New York, 10027, New York, USA James L. Manley Authors * Bin Tian View author publications You can also search for this author inPubMed Google Scholar * James L. Manley

View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Bin Tian or James L. Manley. ETHICS DECLARATIONS COMPETING

INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION S1 (BOX) Variation in alternative polyadenylation across species (PDF 122

kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 GLOSSARY * PUF protein (Pumilio and FBF homology family protein). A member of a

family of RNA-binding proteins that regulate aspects of mRNA metabolism by binding to specific sequences in 3′ untranslated regions. * STAU1-mediated mRNA decay An mRNA decay mechanism in

which RNA structures in the 3′ untranslated region interact with double-stranded RNA-binding protein Staufen homologue 1 (STAU1) to mediate mRNA decay. * AU-rich element-mediated decay mRNA

decay elicited by the presence of AU-rich elements (AREs) in the 3′ untranslated region. * PIWI-interacting RNAs Small non-coding RNAs that form RNA–protein complexes with PIWI proteins to

silence transposable elements in germline cells of metazoans. * Non-stop decay An mRNA decay mechanism that specifically degrades mRNAs without a stop codon. * Exosome A nuclear or

cytoplasmic multiprotein complex that degrades mRNAs through the activity of 3′-to-5′ exoribonucleases. * Non-canonical PAPs (Non-canonical poly(A) polymerases). Enzymes that have distinct

structural features and are capable of synthesizing poly(A) tails but are not typically associated with the polyadenylation machinery. * Paused Pol II (Paused RNA polymerase II). Pol II that

has paused in the promoter-proximal region of the mRNA and is poised for productive elongation. * Paraspeckle A dynamic nuclear compartment composed of RNA-binding proteins and RNAs. The

functions of paraspeckles are not entirely clear. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tian, B., Manley, J. Alternative polyadenylation of

mRNA precursors. _Nat Rev Mol Cell Biol_ 18, 18–30 (2017). https://doi.org/10.1038/nrm.2016.116 Download citation * Published: 28 September 2016 * Issue Date: January 2017 * DOI:

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