RNA‐binding Proteins: Regulation of mRNA Splicing, Export and Decay


Mammalian messenger ribonucleic acid (mRNA)‐binding proteins regulate gene expression at several steps including pre‐mRNA processing, nucleocytoplasmic export and degradation.

Keywords: pre‐mRNA processing; mRNA transport; mRNA stability; RNA splicing; RNA‐binding proteins; nonsense‐mediated mRNA decay; exon‐junction complex

Figure 1.

Pre‐mRNA splicing. Mammalian pre‐mRNAs contain a 5′ cap (m7G), a 5′ untranslated region (5′ UTR), coding regions (numbered 1, 2 and 3) interrupted by noncoding regions called introns, a 3′ untranslated region (3′ UTR) and a poly(A) tail. (CBC) and poly(A)‐binding protein (PABP) interact with the 5′ cap and 3′ poly(A) tail, respectively, where they serve to protect the mRNA from decay. The exons are joined together by a complex splicing process initiated by binding of U1 snRNP (U1) to the 5′ splice site (5′ SS). This is followed by the binding of the branchpoint binding protein (BBP) to the branchpoint, and U2 auxiliary factors U2AF 65 (U2 65) and U2AF 35 (U2 35) to the polypyrimidine tract just upstream of the 3′ splice site (3′ SS). SR proteins (SR) are RNA‐binding proteins that are thought to help recruit these splicing factors to pre‐mRNA. Other molecules involved in RNA splicing described in the text are not shown here. The exon junction complex (EJC) is a multiprotein complex deposited near exon–exon junctions after RNA splicing. It appears to facilitate mRNA export and play a critical role in the NMD RNA surveillance pathway. The positions of the start (AUG) and stop (stop sign) codons are marked.

Figure 2.

Nuclear mRNA export and mRNA decay in the cytoplasm. Nucleocytoplasmic export of mRNA requires its interaction with mRNA‐binding proteins (collectively known as an mRNA–protein complex (mRNP)), which in turn interact with nucleoporins lining the nuclear pore. TAP, a component of the EJC, assists in the movement of mRNP through the nuclear pore. Evidence suggests that the first round of translation ejects the EJC and reorganizes the mRNP in a manner that brings the 5′ and the 3′ ends of the mRNA together to form a circular mRNP complex (this first round of translation is pictured as occurring in the cytoplasm but it may also occur in the nucleus). RNA circularizaton allows for more efficient translation by ribosomes. The poly(A) tail of cytoplasmic mRNAs is degraded by poly(A)‐specific ribonucleases (e.g. PARN) at a rate dependent on intrinsic features of the mRNA and specific RNA‐binding proteins that bind to the 3′ UTR. One class of RNA‐binding proteins that regulate deadenylation is ARE‐binding proteins (AUBPs). AUBPs can also trigger mRNA decay by recruiting the exosome, a multiprotein complex that has multiple 3′–5′ nucleases that degrade the body of RNAs. Decapping enzymes, including those associated with the exosome (e.g. DcpS) degrade the 5′ cap.



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Gudikote, Jayanthi P, and Wilkinson, Miles F(Jan 2006) RNA‐binding Proteins: Regulation of mRNA Splicing, Export and Decay. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005982]