3' RNA uridylation in epitranscriptomics, gene regulation, and disease

Miriam R. Menezes, Julien Balzeau, John P. Hagan

Research output: Contribution to journalReview article

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Abstract

Emerging evidence implicates a wide range of post-transcriptional RNA modifications that play crucial roles in fundamental biological processes including regulating gene expression. Collectively, they are known as epitranscriptomics. Recent studies implicate 3' RNA uridylation, the non-templated addition of uridine(s) to the terminal end of RNA, as a key player in epitranscriptomics. In this review, we describe the functional roles and significance of 3' terminal RNA uridylation that has diverse functions in regulating both mRNAs and non-coding RNAs. In mammals, three Terminal Uridylyl Transferases (TUTases) are primarily responsible for 3' RNA uridylation. These enzymes are also referred to as polyU polymerases. TUTase 1 (TUT1) is implicated in U6 snRNA maturation via uridylation. The TUTases TUT4 and/or TUT7 are the predominant mediators of all other cellular uridylation. Terminal uridylation promotes turnover for many polyadenylated mRNAs, replication-dependent histone mRNAs that lack polyA-tails, and aberrant structured noncoding RNAs. In addition, uridylation regulates biogenesis of a subset of microRNAs and generates isomiRs, sequent variant microRNAs that have altered function in specific cases. For example, the RNA binding protein and proto-oncogene LIN28A and TUT4 work together to polyuridylate pre-let-7, thereby blocking biogenesis and function of the tumor suppressor let-7 microRNA family. In contrast, monouridylation of Group II pre-miRNAs creates an optimal 3' overhang that promotes recognition and subsequent cleavage by the Dicer-TRBP complex that then yields the mature microRNA. Also, uridylation may play a role in non-canonical microRNA biogenesis. The overall significance of 3' RNA uridylation is discussed with an emphasis on mammalian development, gene regulation, and disease, including cancer and Perlman syndrome. We also introduce recent changes to the HUGO-approved gene names for multiple terminal nucleotidyl transferases that affects in part TUTase nomenclature (TUT1/TENT1, TENT2/PAPD4/GLD2, TUT4/ZCCHC11/TENT3A, TUT7/ZCCHC6/TENT3B, TENT4A/PAPD7, TENT4B/PAPD5, TENT5A/FAM46A, TENT5B/FAM46B, TENT5C/FAM46C, TENT5D/FAM46D, MTPAP/TENT6/PAPD1).

LanguageEnglish
Article number61
JournalFrontiers in Molecular Biosciences
Volume5
Issue numberJUL
DOIs
StatePublished - Jul 13 2018

Fingerprint

MicroRNAs
Gene expression
RNA
Transferases
Genes
Untranslated RNA
Messenger RNA
Post Transcriptional RNA Processing
Biological Phenomena
Mammals
RNA-Binding Proteins
Proto-Oncogenes
Uridine
Terminology
Histones
Names
Tail
Tumors
Neoplasms
Gene Expression

Keywords

  • 3' terminal RNA uridylation
  • Cancer
  • DIS3L2
  • LIN28/let-7 pathway
  • Perlman syndrome
  • RNA epitranscritpomics
  • TUTase
  • Wilms tumor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

Cite this

3' RNA uridylation in epitranscriptomics, gene regulation, and disease. / Menezes, Miriam R.; Balzeau, Julien; Hagan, John P.

In: Frontiers in Molecular Biosciences, Vol. 5, No. JUL, 61, 13.07.2018.

Research output: Contribution to journalReview article

Menezes, Miriam R. ; Balzeau, Julien ; Hagan, John P. / 3' RNA uridylation in epitranscriptomics, gene regulation, and disease. In: Frontiers in Molecular Biosciences. 2018 ; Vol. 5, No. JUL.
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