Poly(A) RNA-binding proteins and polyadenosine RNA: new members and novel functions

• Type of Material: Article
• Authors: Callie P. Wigington, Emory University; Kathryn R. Williams, Emory University; Michael P. Meers, University of North Carolina; Gary Bassell, Emory University; Anita Corbett, Emory University
• Language: English
• Date: 2014-09-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 John Wiley & Sons, Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1002/wrna.1233
• Title of Journal or Parent Work: Wiley Interdisciplinary Reviews: RNA
• ISSN: 1757-7004
• Volume: 5
• Issue: 5
• Start Page: 601
• End Page: 622
• Grant/Funding Information: This work was supported by R01 grants from the NIH to AHC (GM058728) and GJB (MH085617) and F31 grants from the NIH to CPW (CA168321) and KRW (MH095266).
• Keywords: IN-VITRO; DENDRITIC BC1 RNA; Life Sciences & Biomedicine; NUCLEAR POLY(A)-BINDING PROTEIN; Science & Technology; TRANSLATION INITIATION-FACTOR; Cell Biology; LA-RELATED PROTEINS; PRE-MESSENGER-RNA; HNRNP Q; EUKARYOTIC TRANSLATION; OCULOPHARYNGEAL MUSCULAR-DYSTROPHY; DEPENDENT TRANSLATION
• Research Categories: Biology, Cell; Chemistry, Biochemistry; Biology, Genetics

Abstract

Poly(A) RNA-binding proteins (Pabs) bind with high affinity and specificity to polyadenosine RNA. Textbook models show a nuclear Pab, PABPN1, and a cytoplasmic Pab, PABPC, where the nuclear PABPN1 modulates poly(A) tail length and the cytoplasmic PABPC stabilizes poly(A) RNA in the cytoplasm and also enhances translation. While these conventional roles are critically important, the Pab family has expanded recently both in number and in function. A number of novel roles have emerged for both PAPBPN1 and PABPC that contribute to the fine-tuning of gene expression. Furthermore, as the characterization of the nucleic acid binding properties of RNA-binding proteins advances, additional proteins that show high affinity and specificity for polyadenosine RNA are being discovered. With this expansion of the Pab family comes a concomitant increase in the potential for Pabs to modulate gene expression. Further complication comes from an expansion of the potential binding sites for Pab proteins as revealed by an analysis of templated polyadenosine stretches present within the transcriptome. Thus, Pabs could influence mRNA fate and function not only by binding to the nontemplated poly(A) tail but also to internal stretches of adenosine. Understanding the diverse functions of Pab proteins is not only critical to understand how gene expression is regulated but also to understand the molecular basis for tissue-specific diseases that occur when Pab proteins are altered. Here we describe both conventional and recently emerged functions for PABPN1 and PABPC and then introduce and discuss three new Pab family members, ZC3H14, hnRNP-Q1, and LARP4.