期刊
FRONTIERS IN GENETICS
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2018.00538
关键词
terminal uridylyltransferase; TUTase; TUT1; TUT4/7; U6 snRNA; let-7; biogenesis; splicing
资金
- Funding Program for Next Generation World-Leading Researchers of JSPS [LS135]
- JSPS [26113002]
- Takeda Science Foundation
- Japan Foundation for Applied Enzymology
- Terumo Foundation for Life Science and Art
- Princess Takamatsu Cancer Research Foundation
- [18H03980]
- Grants-in-Aid for Scientific Research [26113002] Funding Source: KAKEN
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 let-7 (pre-let-7). Let-7 RNA is broadly expressed in somatic cells and regulates cellular proliferation and differentiation. Mono-uridylylation of pre-let-7 by TUT4/7 promotes subsequent Dicer processing to up-regulate let-7 biogenesis. Oligo-uridylylation of pre-let-7 by TUT4/7 is dependent on an RNA-binding protein, Lin28. Oligo-uridylylated pre-let-7 is less responsive to processing by Dicer and degraded by an exonuclease DIS3L2. As a result, let-7 expression is repressed. Uridylylation of pre-let-7 depends on the context of the 3'-region of pre-let-7 and cell type. In this review, we focus on the 3' uridylylation of U6 snRNA and pre-let-7, 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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