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Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation

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Science  19 Jul 2018:
eaam5794
DOI: 10.1126/science.aam5794

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Abstract

RNA tails play integral roles in the regulation of mRNA translation and decay. Guanylation of poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, favoring guanosine. A single guanosine is sufficient to impede deadenylase CCR4-NOT which trims the tail and exposes guanosine at the 3′ end. Consistently, depletion of TENT4A/B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A/B produce a mixed tail which shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of post-transcriptional gene regulation.

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