MyoD induced enhancer RNA interacts with hnRNPL to activate target gene transcription during myogenic differentiation

Abstract

Emerging evidence supports roles of enhancer RNAs (eRNAs) in regulating target gene. Here, we study eRNA regulation and function during skeletal myoblast differentiation. We provide a panoramic view of enhancer transcription and categorization of eRNAs. Master transcription factor MyoD is crucial in activating eRNA production. Super enhancer (se) generated seRNA-1 and -2 promote myogenic differentiation in vitro and in vivo. seRNA-1 regulates expression levels of two nearby genes, myoglobin (Mb) and apolipoprotein L6 (Apol6), by binding to heterogeneous nuclear ribonucleoprotein L (hnRNPL). A CAAA tract on seRNA-1 is essential in mediating seRNA-1/hnRNPL binding and function. Disruption of seRNA-1-hnRNPL interaction attenuates Pol II and H3K36me3 deposition at the Mb locus, in coincidence with the reduction of its transcription. Furthermore, analyses of hnRNPL binding transcriptome-wide reveal its association with eRNAs is a general phenomenon in multiple cells. Collectively, we propose that eRNA-hnRNPL interaction represents a mechanism contributing to target mRNA activation.

Long noncoding RNA SAM promotes myoblast proliferation through stabilizing Sugt1 and facilitating kinetochore assembly

“…5c). No interaction was detected between SAM and a few other known RNA-binding proteins, Hnrnpl 42 , Dnmt3a, and Dnmt3b 15 , suggesting the specificity of the SAM/Sugt1 association. To further confirm their interaction, native RNA immunoprecipitation (RIP) assay was performed using an antibody against Sugt1 (Fig.…”

Our emerging understanding of the roles of long non-coding RNAs in normal liver function, disease, and malignancy

“…This transcriptional activity is primarily J o u r n a l P r e -p r o o f associated with divergently transcribed eRNAs that are not polyadenylated and has been exploited to identify novel enhancer regions by transcriptional profiling of eRNAs [37]. Whether or not these divergent, non-polyadenylated eRNA transcripts have functional activity has been the subject of multiple studies [38][39][40]. However, it is also imaginable that the process of transcription of eRNA at the enhancer region by itself could regulate the enhancer activity through recruitment of activating transcription factors [36].…”

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