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Antisense transcription regulates the expression of sense gene via alternative polyadenylation
Protein & Cell ; (12): 540-552, 2018.
Artigo em Inglês | WPRIM | ID: wpr-758003
ABSTRACT
Natural antisense transcripts (NAT) and alternative polyadenylation (APA) of messenger RNA (mRNA) are important contributors of transcriptome complexity, each playing a critical role in multiple biological processes. However, whether they have crosstalk and function collaboratively is unclear. We discovered that APA enriched in human sense-antisense (S-AS) gene pairs, and finally focused on RNASEH2C-KAT5 S-AS pair for further study. In cis but not in trans over-expression of the antisense KAT5 gene promoted the usage of distal polyA (pA) site in sense gene RNASEH2C, which generated longer 3' untranslated region (3'UTR) and produced less protein, accompanying with slowed cell growth. Mechanistically, elevated Pol II occupancy coupled with SRSF3 could explain the higher usage of distal pA site. Finally, NAT-mediated downregulation of sense gene's protein level in RNASEH2C-KAT5 pair was specific for human rather than mouse, which lacks the distal pA site of RNASEH2C. We provided the first evidence to support that certain gene affected phenotype may not by the protein of its own, but by affecting the expression of its overlapped gene through APA, implying an unexpected view for understanding the link between genotype and phenotype.
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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Transcrição Gênica / RNA Mensageiro / Regulação para Cima / Regulação da Expressão Gênica / RNA Antissenso / Ribonuclease H / Evolução Molecular / Poliadenilação / Proliferação de Células / Células HEK293 Limite: Humanos Idioma: Inglês Revista: Protein & Cell Ano de publicação: 2018 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Transcrição Gênica / RNA Mensageiro / Regulação para Cima / Regulação da Expressão Gênica / RNA Antissenso / Ribonuclease H / Evolução Molecular / Poliadenilação / Proliferação de Células / Células HEK293 Limite: Humanos Idioma: Inglês Revista: Protein & Cell Ano de publicação: 2018 Tipo de documento: Artigo