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脂肪肉瘤中易位/肉瘤中融合蛋白与细胞周期蛋白D1启动子区域转录的lncRNA的结合特异性。

The binding specificity of Translocated in LipoSarcoma/FUsed in Sarcoma with lncRNA transcribed from the promoter region of cyclin D1.

作者信息

Yoneda Ryoma, Suzuki Shiho, Mashima Tsukasa, Kondo Keiko, Nagata Takashi, Katahira Masato, Kurokawa Riki

机构信息

Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241 Japan.

Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011 Japan ; Graduate School of Energy Science, Kyoto University, Gokasho, Uji, Kyoto 611-0011 Japan.

出版信息

Cell Biosci. 2016 Jan 25;6:4. doi: 10.1186/s13578-016-0068-8. eCollection 2016.

DOI:10.1186/s13578-016-0068-8
PMID:26816614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4727290/
Abstract

BACKGROUND

Translocated in LipoSarcoma (TLS, also known as FUsed in Sarcoma) is an RNA/DNA binding protein whose mutation cause amyotrophic lateral sclerosis. In previous study, we demonstrated that TLS binds to long noncoding RNA, promoter-associated ncRNA-D (pncRNA-D), transcribed from the 5' upstream region of cyclin D1 (CCND1), and inhibits the expression of CCND1.

RESULTS

In order to elucidate the binding specificity between TLS and pncRNA-D, we divided pncRNA-D into seven fragments and examined the binding with full-length TLS, TLS-RGG2-zinc finger-RGG3, and TLS-RGG3 by RNA pull down assay. As a result, TLS was able to bind to all the seven fragments, but the fragments containing reported recognition motifs (GGUG and GGU) tend to bind more solidly. The full-length TLS and TLS-RGG2-zinc finger-RGG3 showed a similar interaction with pncRNA-D, but the binding specificity of TLS-RGG3 was lower compared to the full-length TLS and TLS-RGG2-zinc finger-RGG3. Mutation in GGUG and GGU motifs dramatically decreased the binding, and unexpectedly, we could only detect weak interaction with the RNA sequence with stem loop structure.

CONCLUSION

The binding of TLS and pncRNA-D was affected by the presence of GGUG and GGU sequences, and the C terminal domains of TLS function in the interaction with pncRNA-D.

摘要

背景

脂肪肉瘤易位蛋白（TLS，也称为肉瘤融合蛋白）是一种RNA/DNA结合蛋白，其突变会导致肌萎缩侧索硬化症。在先前的研究中，我们证明TLS与从细胞周期蛋白D1（CCND1）5'上游区域转录的长链非编码RNA、启动子相关非编码RNA-D（pncRNA-D）结合，并抑制CCND1的表达。

结果

为了阐明TLS与pncRNA-D之间的结合特异性，我们将pncRNA-D分为七个片段，并通过RNA下拉实验检测其与全长TLS、TLS-RGG2-锌指-RGG3和TLS-RGG3的结合。结果显示，TLS能够与所有七个片段结合，但含有已报道识别基序（GGUG和GGU）的片段往往结合得更牢固。全长TLS和TLS-RGG2-锌指-RGG3与pncRNA-D表现出相似的相互作用，但与全长TLS和TLS-RGG2-锌指-RGG3相比，TLS-RGG3的结合特异性较低。GGUG和GGU基序中的突变显著降低了结合，出乎意料的是，我们只能检测到与具有茎环结构的RNA序列的微弱相互作用。

结论

TLS与pncRNA-D的结合受GGUG和GGU序列的影响，且TLS的C末端结构域在与pncRNA-D的相互作用中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/fce5102a4f6f/13578_2016_68_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/07427a9349ed/13578_2016_68_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/b8c814d6f746/13578_2016_68_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/f3749728ffb3/13578_2016_68_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/a7d8ae35355d/13578_2016_68_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/fce5102a4f6f/13578_2016_68_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/07427a9349ed/13578_2016_68_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/b8c814d6f746/13578_2016_68_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/f3749728ffb3/13578_2016_68_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/a7d8ae35355d/13578_2016_68_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/4727290/fce5102a4f6f/13578_2016_68_Fig5_HTML.jpg

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