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Function and Regulation of Human Terminal Uridylyltransferases

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Journal Front Genet
Date 2018 Nov 29
PMID 30483311
Citations 19
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Abstract

RNA uridylylation plays a pivotal role in the biogenesis and metabolism of functional RNAs, and regulates cellular gene expression. RNA uridylylation is catalyzed by a subset of proteins from the non-canonical terminal nucleotidyltransferase family. In human, three proteins (TUT1, TUT4, and TUT7) have been shown to exhibit template-independent uridylylation activity at 3'-end of specific RNAs. TUT1 catalyzes oligo-uridylylation of U6 small nuclear (sn) RNA, which catalyzes mRNA splicing. Oligo-uridylylation of U6 snRNA is required for U6 snRNA maturation, U4/U6-di-snRNP formation, and U6 snRNA recycling during mRNA splicing. TUT4 and TUT7 catalyze mono- or oligo-uridylylation of precursor (). RNA is broadly expressed in somatic cells and regulates cellular proliferation and differentiation. Mono-uridylylation of by TUT4/7 promotes subsequent Dicer processing to up-regulate biogenesis. Oligo-uridylylation of by TUT4/7 is dependent on an RNA-binding protein, Lin28. Oligo-uridylylated is less responsive to processing by Dicer and degraded by an exonuclease DIS3L2. As a result, expression is repressed. Uridylylation of depends on the context of the 3'-region of and cell type. In this review, we focus on the 3' uridylylation of U6 snRNA and , and describe the current understanding of mechanism of activity and regulation of human TUT1 and TUT4/7, based on their crystal structures that have been recently solved.

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