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TUT7 和 3'hExo 的敲除表明它们在组蛋白 mRNA 的维持和降解中合作。

Knockouts of TUT7 and 3'hExo show that they cooperate in histone mRNA maintenance and degradation.

机构信息

Division of Medicinal Chemistry and Chemical Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Integrated Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

出版信息

RNA. 2022 Nov;28(11):1519-1533. doi: 10.1261/rna.079233.122. Epub 2022 Aug 30.

DOI:10.1261/rna.079233.122
PMID:36041871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9745837/
Abstract

Metazoan histone mRNAs are the only cellular eukaryotic mRNAs that are not polyadenylated, ending instead in a conserved stem-loop. SLBP is bound to the 3' end of histone mRNAs and is required for translation of histone mRNA. The expression of histone mRNAs is tightly cell-cycle regulated. A major regulatory step is rapid degradation of histone mRNA at the end of S-phase or when DNA synthesis is inhibited in S-phase. 3'hExo, a 3' to 5' exonuclease, binds to the SLBP/SL complex and trims histone mRNA to 3 nt after the stem-loop. Together with a terminal uridyl transferase, 3'hExo maintains the length of the histone mRNA during S-phase. 3'hExo is essential for initiating histone mRNA degradation on polyribosomes, initiating degradation into the 3' side of the stem-loop. There is extensive uridylation of degradation intermediates in the 3' side of the stem when histone mRNA is degraded. Here, we knocked out TUT7 and 3'hExo and we show that both modification of histone mRNA during S-phase and degradation of histone mRNA involve the interaction of 3'hExo, and a specific TUTase, TENT3B (TUT7, ZCCHC6). Knockout of 3'hExo prevents the initiation of 3' to 5' degradation, stabilizing histone mRNA, whereas knockout of TUT7 prevents uridylation of the mRNA degradation intermediates, slowing the rate of degradation. In synchronized 3'hExo KO cells, histone mRNA degradation is delayed, but the histone mRNA is degraded prior to mitosis by a different pathway.

摘要

后生动物组蛋白 mRNA 是唯一不进行多聚腺苷酸化、在保守茎环结构末端终止的真核细胞 mRNA。SLBP 与组蛋白 mRNA 的 3' 端结合，是组蛋白 mRNA 翻译所必需的。组蛋白 mRNA 的表达受到严格的细胞周期调控。一个主要的调控步骤是在 S 期结束时或当 DNA 合成在 S 期被抑制时，快速降解组蛋白 mRNA。3' hExo 是一种 3' 到 5' 的外切核酸酶，与 SLBP/SL 复合物结合，并将组蛋白 mRNA 修剪至茎环结构后 3nt。与端粒尿苷转移酶一起，3' hExo 在 S 期内维持组蛋白 mRNA 的长度。3' hExo 对于在多核糖体上起始组蛋白 mRNA 的降解、在茎环结构的 3' 侧起始降解是必不可少的。当组蛋白 mRNA 降解时，在茎环结构的 3' 侧有大量的降解中间物发生尿苷酸化。在这里，我们敲除了 TUT7 和 3' hExo，我们表明，S 期内组蛋白 mRNA 的修饰和组蛋白 mRNA 的降解都涉及 3' hExo 的相互作用，以及一种特定的 TUTase，TENT3B（TUT7，ZCCHC6）。3' hExo 的敲除阻止了 3' 到 5' 降解的起始，稳定了组蛋白 mRNA，而 TUT7 的敲除阻止了 mRNA 降解中间物的尿苷酸化，从而降低了降解速度。在同步化的 3' hExo KO 细胞中，组蛋白 mRNA 的降解被延迟，但在有丝分裂前，组蛋白 mRNA 通过另一种途径被降解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/7662c5b34c14/1519f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/269935c9db3c/1519f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/a3d859008661/1519f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/339cd6098a0f/1519f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/1851b8691e70/1519f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/51ce47185176/1519f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/e05c7b4bd573/1519f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/8817e4594160/1519f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/7662c5b34c14/1519f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/269935c9db3c/1519f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/a3d859008661/1519f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/339cd6098a0f/1519f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/1851b8691e70/1519f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/51ce47185176/1519f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/e05c7b4bd573/1519f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/8817e4594160/1519f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f28/9745837/7662c5b34c14/1519f07.jpg

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