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TUT7催化组蛋白mRNA 3'端的尿苷酸化，使其快速降解。

TUT7 catalyzes the uridylation of the 3' end for rapid degradation of histone mRNA.

作者信息

Lackey Patrick E, Welch Joshua D, Marzluff William F

机构信息

Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

出版信息

RNA. 2016 Nov;22(11):1673-1688. doi: 10.1261/rna.058107.116. Epub 2016 Sep 8.

DOI:10.1261/rna.058107.116
PMID:27609902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5066620/
Abstract

The replication-dependent histone mRNAs end in a stem-loop instead of the poly(A) tail present at the 3' end of all other cellular mRNAs. Following processing, the 3' end of histone mRNAs is trimmed to 3 nucleotides (nt) after the stem-loop, and this length is maintained by addition of nontemplated uridines if the mRNA is further trimmed by 3'hExo. These mRNAs are tightly cell-cycle regulated, and a critical regulatory step is rapid degradation of the histone mRNAs when DNA replication is inhibited. An initial step in histone mRNA degradation is digestion 2-4 nt into the stem by 3'hExo and uridylation of this intermediate. The mRNA is then subsequently degraded by the exosome, with stalled intermediates being uridylated. The enzyme(s) responsible for oligouridylation of histone mRNAs have not been definitively identified. Using high-throughput sequencing of histone mRNAs and degradation intermediates, we find that knockdown of TUT7 reduces both the uridylation at the 3' end as well as uridylation of the major degradation intermediate in the stem. In contrast, knockdown of TUT4 did not alter the uridylation pattern at the 3' end and had a small effect on uridylation in the stem-loop during histone mRNA degradation. Knockdown of 3'hExo also altered the uridylation of histone mRNAs, suggesting that TUT7 and 3'hExo function together in trimming and uridylating histone mRNAs.

摘要

依赖复制的组蛋白mRNA在3'端以茎环结构结尾，而非像所有其他细胞mRNA那样具有poly(A)尾。加工后，组蛋白mRNA的3'端在茎环结构之后被修剪至3个核苷酸（nt），如果mRNA被3'hExo进一步修剪，该长度会通过添加非模板尿苷来维持。这些mRNA受到严格的细胞周期调控，一个关键的调控步骤是当DNA复制受到抑制时，组蛋白mRNA迅速降解。组蛋白mRNA降解的第一步是3'hExo将茎环结构内2 - 4 nt处的mRNA消化，并对该中间体进行尿苷酸化。随后，mRNA被外切体降解，停滞的中间体也会被尿苷酸化。负责组蛋白mRNA寡聚尿苷酸化的酶尚未被明确鉴定。通过对组蛋白mRNA及其降解中间体进行高通量测序，我们发现敲低TUT7会降低3'端的尿苷酸化以及茎环结构中主要降解中间体的尿苷酸化。相反，敲低TUT4不会改变3'端的尿苷酸化模式，并且在组蛋白mRNA降解过程中对茎环结构中的尿苷酸化影响较小。敲低3'hExo也会改变组蛋白mRNA的尿苷酸化，这表明TUT7和3'hExo在修剪和尿苷酸化组蛋白mRNA过程中共同发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/8d2d4aae2c66/1673F7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/114874f375bb/1673F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/8f5239acbc09/1673F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/8a16d15093e5/1673F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/1a44ec2bc557/1673F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/4802ce5d6848/1673F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/08a7bbdee6d8/1673F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/8d2d4aae2c66/1673F7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/114874f375bb/1673F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/8f5239acbc09/1673F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/8a16d15093e5/1673F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/1a44ec2bc557/1673F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/4802ce5d6848/1673F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/08a7bbdee6d8/1673F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78a0/5066620/8d2d4aae2c66/1673F7.jpg

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