An XIST-related small RNA regulates KRAS G-quadruplex formation beyond X-inactivation.
Oncotarget
; 7(52): 86713-86729, 2016 Dec 27.
Article
em En
| MEDLINE
| ID: mdl-27880931
ABSTRACT
X-inactive-specific transcript (XIST), a long non-coding RNA, is essential for the initiation of X-chromosome inactivation. However, little is known about other roles of XIST in the physiological process in eukaryotic cells. In this study, the bioinformatics approaches revealed XIST could be processed into a small non-coding RNA XPi2. The XPi2 RNA was confirmed by a northern blot assay; its expression was gender-independent, suggesting the role of XPi2 was beyond X-chromosome inactivation. The pull-down assay combined with LC-MS-MS identified two XPi2-associated proteins, nucleolin and hnRNP A1, connected to the formation of G-quadruplex. Moreover, the microarray data showed the knockdown of XPi2 down-regulated the KRAS pathway. Consistently, we tested the expression of ten genes, including KRAS, which was correlated with a G-quadruplex formation and found the knockdown of XPi2 caused a dramatic decrease in the transcription level of KRAS among the ten genes. The results of CD/NMR assay also supported the interaction of XPi2 and the polypurine-polypyrimidine element of KRAS. Accordingly, XPi2 may stimulate the KRAS expression by attenuating G-quadruplex formation. Our present work sheds light on the novel role of small RNA XPi2 in modulating the G-quadruplex formation which may play some essential roles in the KRAS- associated carcinogenesis.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Proteínas Proto-Oncogênicas p21(ras)
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Inativação do Cromossomo X
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Quadruplex G
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Pequeno RNA não Traduzido
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RNA Longo não Codificante
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Taiwan