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Biochim Biophys Acta. 2012 Jun;1819(6):546-54. doi: 10.1016/j.bbagrm.2012.03.006. Epub 2012 Mar 28.

The long and the short of it: the role of the zinc finger polyadenosine RNA binding protein, Nab2, in control of poly(A) tail length.

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Department of biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.


In eukaryotic cells, addition of poly(A) tails to transcripts by 3'-end processing/polyadenylation machinery is a critical step in gene expression. The length of the poly(A) tail influences the stability, nuclear export and translation of mRNA transcripts. Control of poly(A) tail length is thus an important mechanism to regulate the abundance and ultimate translation of transcripts. Understanding the global regulation of poly(A) tail length will require dissecting the contributions of enzymes, regulatory factors, and poly(A) binding proteins (Pabs) that all cooperate to regulate polyadenylation. A recent addition to the Pab family is the CCCH-type zinc finger class of Pabs that includes S. cerevisiae Nab2 and its human counterpart, ZC3H14. In S. cerevisiae, Nab2 is an essential nuclear Pab implicated in both poly(A) RNA export from the nucleus and control of poly(A) tail length. Consistent with an important role in regulation of poly(A) tail length, depletion of Nab2 from yeast cells results in hyperadenylation of poly(A) RNA. In this review, we focus on the role of Nab2 in poly(A) tail length control and speculate on potential mechanisms by which Nab2 could regulate poly(A) tail length based on reported physical and genetic interactions. We present models, illustrating how Nab2 could regulate poly(A) tail length by limiting polyadenylation and/or enhancing trimming. Given that mutation of the gene encoding the human Nab2 homologue, ZC3H14, causes a form of autosomal recessive intellectual disability, we also speculate on how mutations in a gene encoding a ubiquitously expressed Pab lead specifically to neurological defects. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.

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