MBNL1 Regulates the Expression and Alternative Splicing of Genes Enriched in Cell Adhesion and Apoptosis

Abstract Muscleblind Like Splicing Regulator 1 (MBNL1), one canonical RNA binding protein (RBP), plays important roles in the regulation of the alternative splicing (AS) on pre-mRNAs. MBNL1 has traditionally been considered involved in the pathogenesis of myotonic dystrophy. Recent researches point out that MBNL1 has an effect on cancer progress, but the underlying mechanisms are unclear. In this study, we obtained the regulated transcriptome profile of MBNL1 in HeLa cells by RNA-seq analysis. The results showed that the knockdown of MBNL1 promoted cell proliferation while inhibited apoptosis. We found 398 genes were differentially up-regulated and 277 down-regulated by MBNL1 knockdown (KD). The differentially expressed genes (DEGs) regulated by MBNL1-KD were enriched in the signal pathways of homophilic cell adhesion, apoptotic process, extracellular matrix organization and cell migration. Systematical AS analysis revealed 504 MBNL1-regulated AS events. The regulated alternative splicing genes (RASGs) were enriched in the signal pathways of apoptotic signaling pathway, positive regulation of apoptotic process, adherent junction, fatty acid elongation and DNA repair. In summary, our results demonstrate that the knockdown of MBNL1 have significant effects on cell proliferation and apoptosis by regulating the expression and alternative splicing of associated genes, illustrating the possible molecular mechanisms of MBNL1 in cancer pathogenesis and progression and other diseases..

Medienart:

Preprint

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

ResearchSquare.com - (2021) vom: 30. Juli Zur Gesamtaufnahme - year:2021

Sprache:

Englisch

Beteiligte Personen:

Liu, Meijia [VerfasserIn]
Song, Xianjing [VerfasserIn]
Li, Longbo [VerfasserIn]
Song, Chunli [VerfasserIn]
Shi, Yongfeng [VerfasserIn]

Links:

Volltext [kostenfrei]

doi:

10.21203/rs.3.rs-731723/v1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XRA034008039