<i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation
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 st...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/108 |
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| author | Keisuke Hitachi Yuri Kiyofuji Masashi Nakatani Kunihiro Tsuchida |
| author_facet | Keisuke Hitachi Yuri Kiyofuji Masashi Nakatani Kunihiro Tsuchida |
| author_sort | Keisuke Hitachi |
| collection | DOAJ |
| description | 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 <i>Myoparr</i> binding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression of <i>myogenin</i> at the transcriptional level. The hnRNPK-binding region of <i>Myoparr</i> was required to repress <i>myogenin</i> expression. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in a <i>Myoparr</i>-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. |
| first_indexed | 2024-03-10T03:40:30Z |
| format | Article |
| id | doaj.art-69034626677445fc83b52e9c6d742984 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:40:30Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-69034626677445fc83b52e9c6d7429842023-11-23T11:34:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123110810.3390/ijms23010108<i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell DifferentiationKeisuke Hitachi0Yuri Kiyofuji1Masashi Nakatani2Kunihiro Tsuchida3Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake 470-1192, JapanDivision for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake 470-1192, JapanFaculty of Rehabilitation and Care, Seijoh University, Tokai 476-8588, JapanDivision for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake 470-1192, JapanRNA-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 <i>Myoparr</i> binding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression of <i>myogenin</i> at the transcriptional level. The hnRNPK-binding region of <i>Myoparr</i> was required to repress <i>myogenin</i> expression. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in a <i>Myoparr</i>-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.https://www.mdpi.com/1422-0067/23/1/108transcriptional regulationmyogenic differentiationRNA-binding proteinendoplasmic reticulum stress |
| spellingShingle | Keisuke Hitachi Yuri Kiyofuji Masashi Nakatani Kunihiro Tsuchida <i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation International Journal of Molecular Sciences transcriptional regulation myogenic differentiation RNA-binding protein endoplasmic reticulum stress |
| title | <i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation |
| title_full | <i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation |
| title_fullStr | <i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation |
| title_full_unstemmed | <i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation |
| title_short | <i>Myoparr</i>-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation |
| title_sort | i myoparr i associated and independent multiple roles of heterogeneous nuclear ribonucleoprotein k during skeletal muscle cell differentiation |
| topic | transcriptional regulation myogenic differentiation RNA-binding protein endoplasmic reticulum stress |
| url | https://www.mdpi.com/1422-0067/23/1/108 |
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