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mRNA 的神经元特异性微外显子剪接直接受 SRRM4/nSR100 的调控。

Neuronal-specific microexon splicing of mRNA is directly regulated by SRRM4/nSR100.

机构信息

German Cancer Consortium (DKTK) partner site Freiburg, German Cancer Research Center (DKFZ) and Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.

EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, The Barcelona Institute for Science and Technology, Barcelona, Spain.

出版信息

RNA Biol. 2020 Jan;17(1):62-74. doi: 10.1080/15476286.2019.1667214. Epub 2019 Sep 27.

DOI:10.1080/15476286.2019.1667214
PMID:31559909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6948980/
Abstract

Neuronal microexons represent the most highly conserved class of alternative splicing events and their timed expression shapes neuronal biology, including neuronal commitment and differentiation. The six-nt microexon 34' is included in the neuronal form of  mRNA, which encodes the largest subunit of the basal transcription factor TFIID. In this study, we investigate the tissue distribution of mRNA and protein and the mechanism responsible for its neuronal-specific splicing. Using isoform-specific RNA probes and antibodies, we observe that canonical TAF1 and TAF1-34' have different distributions in the brain, which distinguish proliferating from post-mitotic neurons. Knockdown and ectopic expression experiments demonstrate that the neuronal-specific splicing factor SRRM4/nSR100 promotes the inclusion of microexon 34' into mRNA, through the recognition of UGC sequences in the poly-pyrimidine tract upstream of the regulated microexon. These results show that SRRM4 regulates temporal and spatial expression of alternative mRNAs to generate a neuronal-specific TFIID complex.

摘要

神经元微外显子代表了最保守的可变剪接事件类别，其表达时间决定了神经元生物学特性，包括神经元的定向和分化。六核苷酸微外显子 34' 包含在编码基础转录因子 TFIID 大亚基的 mRNA 的神经元形式中。在这项研究中，我们研究了 mRNA 和蛋白质的组织分布以及负责其神经元特异性剪接的机制。使用同种型特异性 RNA 探针和抗体，我们观察到经典的 TAF1 和 TAF1-34' 在大脑中的分布不同，这可以区分增殖神经元和有丝分裂后神经元。敲低和异位表达实验表明，神经元特异性剪接因子 SRRM4/nSR100 通过识别受调控微外显子上游多嘧啶序列中的 UGC 序列，促进微外显子 34' 纳入 mRNA。这些结果表明，SRRM4 调节可变剪接 mRNAs 的时空表达，以产生神经元特异性 TFIID 复合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/a6a42398c5e2/krnb-17-01-1667214-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/9dfdc323f2ce/krnb-17-01-1667214-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/9717272557f6/krnb-17-01-1667214-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/155f5fc40066/krnb-17-01-1667214-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/4b3378ca57dc/krnb-17-01-1667214-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/d5115a82c18d/krnb-17-01-1667214-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/a6a42398c5e2/krnb-17-01-1667214-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/9dfdc323f2ce/krnb-17-01-1667214-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/9717272557f6/krnb-17-01-1667214-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/155f5fc40066/krnb-17-01-1667214-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/4b3378ca57dc/krnb-17-01-1667214-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/d5115a82c18d/krnb-17-01-1667214-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc36/6948980/a6a42398c5e2/krnb-17-01-1667214-g006.jpg

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