期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/ijms23010108
关键词
transcriptional regulation; myogenic differentiation; RNA-binding protein; endoplasmic reticulum stress
资金
- JSPS KAKENHI [19H03427, 20K07315]
- NCNP
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- [2-5]
- Grants-in-Aid for Scientific Research [19H03427, 20K07315] Funding Source: KAKEN
This study reveals the multiple inhibitory functions of heterogeneous nuclear ribonucleoprotein K (hnRNPK) during myogenic differentiation, indicating the importance of analyzing lncRNA-binding proteins for understanding the physiological functions of lncRNAs and the multiple functions of RBPs.
RNA-binding proteins (RBPs) regulate cell physiology via the formation of ribonucleic-protein complexes with coding and non-coding RNAs. RBPs have multiple functions in the same cells; however, the precise mechanism through which their pleiotropic functions are determined remains unknown. In this study, we revealed the multiple inhibitory functions of heterogeneous nuclear ribonucleoprotein K (hnRNPK) for myogenic differentiation. We first identified hnRNPK as a lncRNA Myoparr binding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression of myogenin at the transcriptional level. The hnRNPK-binding region of Myoparr was required to repress myogenin expression. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in a Myoparr-independent manner. Mechanistically, hnRNPK regulated the eIF2 alpha/Atf4 pathway, one branch of the intrinsic pathways of the endoplasmic reticulum sensors, in differentiating myoblasts. Thus, our findings demonstrate that hnRNPK plays lncRNA-associated and -independent multiple roles during myogenic differentiation, indicating that the analysis of lncRNA-binding proteins will be useful for elucidating both the physiological functions of lncRNAs and the multiple functions of RBPs.
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