PT  - JOURNAL ARTICLE
AU  - Keisuke Hitachi
AU  - Yuri Kiyofuji
AU  - Masashi Nakatani
AU  - Kunihiro Tsuchida
TI  - <em>Myoparr</em>-associated and -independent multiple roles of heterogeneous nuclear ribonucleoprotein K during skeletal muscle cell differentiation
AID  - 10.1101/2021.07.09.451593
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.09.451593
4099  - http://biorxiv.org/content/early/2021/09/16/2021.07.09.451593.short
4100  - http://biorxiv.org/content/early/2021/09/16/2021.07.09.451593.full
AB  - 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 eIF2α/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.Competing Interest StatementThe authors have declared no competing interest.