3' RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease.

3' RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease.
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DOI:
10.3389/fmolb.2018.00061
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发表时间:
2018
影响因子:
5
通讯作者:
Hagan JP
Hagan JP
中科院分区:
生物学3区
文献类型:
--
作者:
Menezes MR;Balzeau J;Hagan JP

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新出现的证据表明,广泛的转录后RNA修饰在包括调节基因表达在内的基本生物学过程中起着至关重要的作用。总的来说,它们被称为epitranscriptomics。最近的研究表明,3′ RNA尿苷酸化,即非模板化的尿苷添加到RNA末端,是表位转录组学中的关键参与者。本文综述了RNA 3′端尿苷化在调节mRNA和非编码RNA中的作用及其意义。在哺乳动物中,三种末端尿苷酰转移酶(TUTases)主要负责3′ RNA尿苷化。这些酶也被称为polyU聚合酶。TUTase 1(TUT 1)通过尿苷酸化参与U6 snRNA成熟。TUTases TUT 4和/或TUT 7是所有其他细胞尿苷酸化的主要介质。末端尿苷酸化促进许多聚腺苷酸化mRNA、缺乏polyA尾的复制依赖性组蛋白mRNA和异常结构的非编码RNA的周转。此外,尿苷酸化调节一部分microRNA的生物发生,并产生在特定情况下具有改变的功能的isomiR、β变体microRNA。例如,RNA结合蛋白和原癌基因LIN 28 A和TUT 4共同作用以使pre-let-7多聚尿苷酸化,从而阻断肿瘤抑制因子let-7 microRNA家族的生物发生和功能。相比之下,II组pre-miRNA的单核苷酸化产生了最佳的3′突出端,其促进Dicer-TRBP复合物的识别和随后的切割,然后产生成熟的microRNA。此外,尿苷酸化可能在非典型microRNA生物发生中起作用。3′ RNA尿苷酸化的整体意义进行了讨论,重点是哺乳动物的发育,基因调控和疾病,包括癌症和帕尔曼综合征。我们还介绍了HUGO批准的多末端核苷酸转移酶基因名称的最新变化,这些基因名称部分影响TUTase命名法(TUT 1/TENT 1,TENT 2/PAPD 4/GLD 2,TUT 4/ZCCHC 11/TENT 3A,TUT 7/ZCCHC 6/TENT 3B,TENT 4A/PAPD 7,TENT 4 B/PAPD 5,TENT 5A/FAM 46 A,TENT 5 B/FAM 46 B,TENT 5C/FAM 46 C,TENT 5D/FAM 46 D,MTPAP/TENT 6/PAPD 1)。
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).
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