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A tale of non-canonical tails: gene regulation by post-transcriptional RNA tailing

Nature Reviews Molecular Cell Biology volume 21, pages 542–556 (2020)Cite this article

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Abstract

RNA tailing, or the addition of non-templated nucleotides to the 3′ end of RNA, is the most frequent and conserved type of RNA modification. The addition of tails and their composition reflect RNA maturation stages and have important roles in determining the fate of the modified RNAs. Apart from canonical poly(A) polymerases, which add poly(A) tails to mRNAs in a transcription-coupled manner, a family of terminal nucleotidyltransferases (TENTs), including terminal uridylyltransferases (TUTs), modify RNAs post-transcriptionally to control RNA stability and activity. The human genome encodes 11 different TENTs with distinct substrate specificity, intracellular localization and tissue distribution. In this Review, we discuss recent advances in our understanding of non-canonical RNA tails, with a focus on the functions of human TENTs, which include uridylation, mixed tailing and post-transcriptional polyadenylation of mRNAs, microRNAs and other types of non-coding RNA.

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Fig. 1: Human terminal nucleotidyltransferases.
Fig. 2: Polyadenylation and mixed tailing of mRNAs by terminal nucleotidyl transferases.
Fig. 3: Uridylation of mRNAs by TUT4 and TUT7.
Fig. 4: Pre-miRNA uridylation by TUT4 and TUT7.

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Acknowledgements

The authors are grateful to the members of their laboratory for helpful discussions and comments, especially to H. Kim, D. Kim, Y.-s. Lee and H. Jang for their insights and suggestions. Work in the laboratory of V.N.K. was supported by the Institute for Basic Science from the Ministry of Science and ICT of Korea (IBS-R008-D1 to S.Y. and V.N.K.).

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  1. Center for RNA Research, Institute for Basic Science, Seoul, Korea

    Sha Yu & V. Narry Kim

  2. School of Biological Sciences, Seoul National University, Seoul, Korea

    V. Narry Kim

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HUGO Gene Nomenclature Committee: https://www.genenames.org/

Glossary

mRNA decay

Post-transcriptional mRNA degradation through decapping, 5′–3′ exonucleolytic decay, deadenylation, 3′–5′ exonucleolytic decay and endonucleolytic cleavage.

Small Cajal body-specific RNAs

(scaRNAs). A class of small nucleolar RNAs that localize to nuclear Cajal bodies and guide 2′-O-methylation and pseudouridylation of certain RNA polymerase II-dependent transcripts.

RNA exosome

A ribonuclease complex with both endoribonucleolytic function and 3′–5′ exoribonucleolytic activity that degrades various types of RNA, including mRNAs, ribosomal RNAs and many species of small RNA.

P granules

Membraneless ribonucleoprotein organelles that form in the germline of Caenorhabditis elegans. P granules are associated with RNA metabolism and their formation is driven by liquid–liquid phase separation.

Zinc finger domain

A small, independently folded domain that coordinates with one or more zinc ions to stabilize its structure; binds DNA, RNA, proteins and/or lipids.

Zinc knuckle domain

A zinc-binding motif; in this context a Cys2HisCys (CCHC)-type zinc finger domain.

Cryptic transcripts

A class of non-coding RNAs that are produced by relaxation of transcriptional control and are rapidly degraded by RNA surveillance pathways.

Ameloblasts

A group of cells that exist only during tooth development and deposit tooth enamel.

External transcribed spacer

A non-functional part of precursor ribosomal RNAs, positioned between the different ribosomal RNA species.

Y RNAs

Highly structured small non-coding RNAs essential for the initiation of chromosomal DNA replication in vertebrates. Humans encode four Y RNAs, which localize to both the nucleus and the cytoplasm.

Vault RNAs

Small non-coding RNA components of the large vault ribonucleoprotein. Vault RNAs are predicted to fold into stem–loop structures, which are processed into small vault RNAs through a Dicer-dependent mechanism.

7SL RNAs

Abundant cytoplasmic non-coding RNAs that function in protein secretion as the scaffold that makes possible the assembly of the signal recognition particle complex.

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Yu, S., Kim, V.N. A tale of non-canonical tails: gene regulation by post-transcriptional RNA tailing. Nat Rev Mol Cell Biol 21, 542–556 (2020). https://doi.org/10.1038/s41580-020-0246-8

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