RNA-binding proteins Rbm38 and Rbm24 regulate myogenic differentiation via p21-dependent and -independent regulatory pathways

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 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 via binding to Myoparr. 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 multiple lncRNA-dependent and -independent roles in the inhibition of 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.

Download Full-text

Myoparr-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation

International Journal of Molecular Sciences ◽

10.3390/ijms23010108 ◽

2021 ◽

Vol 23 (1) ◽

pp. 108

Author(s):

Keisuke Hitachi ◽

Yuri Kiyofuji ◽

Masashi Nakatani ◽

Kunihiro Tsuchida

Keyword(s):

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Myogenic Differentiation ◽

Multiple Roles ◽

Cell Physiology ◽

Transcriptional Level ◽

Multiple Functions ◽

Heterogeneous Nuclear Ribonucleoprotein ◽

Nuclear Ribonucleoprotein

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.

Download Full-text

The Musashi family RNA-binding proteins in stem cells

BioMolecular Concepts ◽

10.1515/bmc.2010.005 ◽

2010 ◽

Vol 1 (1) ◽

pp. 59-66 ◽

Cited By ~ 9

Author(s):

Kenichi Horisawa ◽

Takao Imai ◽

Hideyuki Okano ◽

Hiroshi Yanagawa

Keyword(s):

Progenitor Cells ◽

Translational Regulation ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Regulatory Pathways ◽

Target Mrnas ◽

Action Mechanisms ◽

Neural Stem Progenitor Cells ◽

Novel Target

AbstractThe Musashi family is an evolutionarily conserved group of RNA-binding proteins. In mammal, two members of the group, Msi1 and Msi2, have been identified to date. Msi1 is considered to play roles in maintaining the stem cell status (stemness) of neural stem/progenitor cells in adults and in the development of central nervous system through translational regulation of its target mRNAs, which encode regulators of signal transduction and the cell cycle. Recently, strong expression of Msi1 in various somatic stem/progenitor cells of adult tissues, such as eye, gut, stomach, breast, and hair follicle, has been reported. The protein is also expressed in various cancer cells, and ectopically emerging cells have been found in neural tissues of patients with diseases involving neural disorder, including epilepsy. Many novel target mRNAs and regulatory pathways of Msi1 have been reported in recent years. Here, we present a review of the functions and action mechanisms of Msi1 protein and discuss possible directions for further study.

Download Full-text