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SF2/ASF 自身调控涉及转录后和翻译水平的多层级控制。

SF2/ASF autoregulation involves multiple layers of post-transcriptional and translational control.

机构信息

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.

出版信息

Nat Struct Mol Biol. 2010 Mar;17(3):306-12. doi: 10.1038/nsmb.1750. Epub 2010 Feb 7.

DOI:10.1038/nsmb.1750
PMID:20139984
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2921916/
Abstract

SF2/ASF is a prototypical serine- and arginine-rich protein, with important roles in splicing and other aspects of mRNA metabolism. Splicing factor, arginine/serine-rich 1 (SFRS1), the gene encoding SF2/ASF, is a potent proto-oncogene with abnormal expression in many tumors. We found that SF2/ASF negatively autoregulates its expression to maintain homeostatic levels. We characterized six alternatively spliced SF2/ASF mRNA isoforms: the major isoform encodes full-length protein, whereas the others are either retained in the nucleus or degraded by nonsense-mediated mRNA decay. Unproductive splicing accounts for only part of the autoregulation, which occurs primarily at the translational level. The effect is specific to SF2/ASF and requires RNA recognition motif 2 (RRM2). The ultraconserved 3' untranslated region (UTR) is necessary and sufficient for downregulation. SF2/ASF overexpression shifts the distribution of target mRNA toward monoribosomes, and translational repression is partly independent of Dicer and a 5' cap. Thus, multiple post-transcriptional and translational mechanisms are involved in fine-tuning the expression of SF2/ASF.

摘要

SF2/ASF 是一种典型的丝氨酸/精氨酸丰富蛋白，在剪接和 mRNA 代谢的其他方面发挥重要作用。剪接因子，精氨酸/丝氨酸丰富 1（SFRS1），是编码 SF2/ASF 的基因，是一种潜在的癌基因，在许多肿瘤中表达异常。我们发现 SF2/ASF 通过负反馈自我调节其表达以维持体内平衡水平。我们对六种剪接的 SF2/ASF mRNA 异构体进行了表征：主要异构体编码全长蛋白，而其他异构体则保留在核内或通过无意义介导的 mRNA 降解而降解。非生产性剪接仅占自我调节的一部分，主要发生在翻译水平。这种效应是 SF2/ASF 特有的，需要 RNA 识别基序 2（RRM2）。超保守的 3'非翻译区（UTR）是下调所必需和充分的。SF2/ASF 的过表达将靶 mRNA 的分布推向单核糖体，并且翻译抑制在一定程度上独立于 Dicer 和 5' 帽。因此，多种转录后和翻译机制参与了 SF2/ASF 表达的精细调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/dbae9c30a161/nihms223137f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/669bc45144df/nihms223137f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/7c0b6c617de3/nihms223137f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/ad5cdec3788f/nihms223137f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/47a26c9587aa/nihms223137f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/4e1b1ff02727/nihms223137f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/dbae9c30a161/nihms223137f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/669bc45144df/nihms223137f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/7c0b6c617de3/nihms223137f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/ad5cdec3788f/nihms223137f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/47a26c9587aa/nihms223137f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/4e1b1ff02727/nihms223137f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/381b/2921916/dbae9c30a161/nihms223137f6.jpg

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