Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis.
Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis.
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DOI：
10.1038/nsmb.1874
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发表时间：
2010-08
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
作者：
多能性促进蛋白Lin 28 a和Lin 28 b在未分化胚胎干细胞中作为let-7 miRNA生物合成的转录后阻遏物。成熟let-7a的水平在缺乏Lin 28表达的细胞中显著不同，表明存在额外的转录后调节机制。在这里，我们提出的证据支持hnRNP A1作为let-7a的负调节剂的作用。HnRNP A1结合pri-let-7a-1的保守末端环并抑制Drosha对其的加工。成熟let-7a的水平与体细胞系中的hnRNP A1水平负相关。此外，hnRNP A1耗竭增加了细胞提取物对pri-let-7a-1的处理，而其异位表达降低了体内let-7a的产生。最后，hnRNP A1与let-7a的结合干扰了已知促进let-7a生物合成的KH型剪接调节蛋白KSRP的结合。我们建议，hnRNPA 1和KSRP发挥拮抗作用的转录后调控let-7a的表达。
The pluripotency promoting proteins Lin28a and Lin28b act as posttranscriptional repressors of let-7 miRNA biogenesis in undifferentiated embryonic stem cells. The levels of mature let-7a differ substantially in cells lacking Lin28 expression, indicating the existence of additional mechanism(s) of posttranscriptional regulation. Here, we present evidence supporting a role for hnRNP A1 as a negative regulator of let-7a. HnRNP A1 binds the conserved terminal loop of pri-let-7a-1 and inhibits its processing by Drosha. Levels of mature let-7a negatively correlate with hnRNP A1 levels in somatic cell lines. Furthermore, hnRNP A1 depletion increased pri-let-7a-1 processing by cell extracts, whereas its ectopic expression decreased let-7a production in vivo. Finally, hnRNP A1 binding to let-7a interferes with the binding of the KH-type splicing regulatory protein KSRP, known to promote let-7a biogenesis. We propose that hnRNP A1 and KSRP play antagonistic roles in the posttranscriptional regulation of let-7a expression.
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影响因子：
9.2
作者：
Landthaler, M;Yalcin, A;Tuschl, T
通讯作者：
Tuschl, T
DOI：
10.1007/978-0-387-77374-2_8
发表时间：
2007-01-01
期刊：
ALTERNATIVE SPLICING IN THE POSTGENOMIC ERA
影响因子：
--
作者：
Martinez-Contreras, Rebeca;Cloutier, Philippe;Chabot, Benoit
通讯作者：
Chabot, Benoit
影响因子：
64.8
作者：
Davis, Brandi N.;Hilyard, Aaron C.;Hata, Akiko
通讯作者：
Hata, Akiko
影响因子：
64.8
作者：
Denli, AM;Tops, BBJ;Hannon, GJ
通讯作者：
Hannon, GJ
影响因子：
64.5
作者：
Heo, Inha;Joo, Chirlmin;Kim, V. Narry
通讯作者：
Kim, V. Narry