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 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.
Highlights
Modification of the 3 -end of RNA by template-independent nucleotide addition is a posttranscriptional modification that plays important regulatory roles in gene expression
Human terminal uridylyltransferase (TUTase): Structures and Functions an unstable acceptor stem is modified by CCACCA addition, and the CCACCA tail serves as a degradation signal for cellular RNA decay machinery (Wilusz et al, 2011; Betat and Morl, 2015; Kuhn et al, 2015)
We describe the molecular mechanism and regulation of uridylylation of specific RNAs by human TUT1 and TUT7, based on their structures
Summary
Reviewed by: Tohru Yoshihisa, University of Hyogo, Japan John P. University of Texas Health Science Center at Houston, United States Yuka W.
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