HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA

Mohammad Alinoor Rahman, Akio Masuda, Kenji Ohe, Mikako Ito, David O. Hutchinson, Akila Mayeda, Andrew G. Engel, Kinji Ohno

研究成果: Article

21 引用 (Scopus)

抜粋

CHRNA1 gene, encoding the muscle nicotinic acetylcholine receptor alpha subunit, harbors an inframe exon P3A. Inclusion of exon P3A disables assembly of the acetylcholine receptor subunits. A single nucleotide mutation in exon P3A identified in congenital myasthenic syndrome causes exclusive inclusion of exon P3A. The mutation gains a de novo binding affinity for a splicing enhancing RNA-binding protein, hnRNP LL, and displaces binding of a splicing suppressing RNA-binding protein, hnRNP L. The hnRNP L binds to another splicing repressor PTB through the proline-rich region and promotes PTB binding to the polypyrimidine tract upstream of exon P3A, whereas hnRNP LL lacking the proline-rich region cannot bind to PTB. Interaction of hnRNP L with PTB inhibits association of U2AF 65 and U1 snRNP with the upstream and downstream of P3A, respectively, which causes a defect in exon P3A definition. HnRNP L and hnRNP LL thus antagonistically modulate PTB-mediated splicing suppression of exon P3A.

元の言語English
記事番号2931
ジャーナルScientific reports
3
DOI
出版物ステータスPublished - 25-10-2013

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All Science Journal Classification (ASJC) codes

  • General

これを引用

Rahman, M. A., Masuda, A., Ohe, K., Ito, M., Hutchinson, D. O., Mayeda, A., Engel, A. G., & Ohno, K. (2013). HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA. Scientific reports, 3, [2931]. https://doi.org/10.1038/srep02931