Lionheart LincRNA alleviates cardiac systolic dysfunction under pressure overload
| Autor: | Masahiro Kimura, Tetsushi Nakao, Shin Watanabe, Yoshinori Yoshida, Osamu Baba, Masataka Nishiga, Takeshi Hatani, Tsukasa Inada, Yui Miyasaka, Naoya Sowa, Shinji Ito, Yasuhiro Nakashima, Yasuhide Kuwabara, Shuhei Tsuji, Hisanori Kiryu, Masayasu Izuhara, Koh Ono, Satoshi Koyama, Kazuya Nagao, Yuya Ide, Tomohiro Nishino, Takahiro Horie, Fumiko Nakazeki, Takeshi Kimura |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Systole Biopsy Heart Ventricles Medicine (miscellaneous) 030204 cardiovascular system & hematology Biology Contractile protein General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Myosin medicine Pressure Animals Humans Promoter Regions Genetic lcsh:QH301-705.5 Pressure overload Mice Knockout Heart Dependovirus medicine.disease Long non-coding RNA Cell biology Rats Up-Regulation Mice Inbred C57BL Cardiac hypertrophy 030104 developmental biology Phenotype lcsh:Biology (General) Heart failure biology.protein Long non-coding RNAs RNA Long Noncoding MYH6 General Agricultural and Biological Sciences Protein A |
| Zdroj: | Communications Biology Communications Biology, Vol 3, Iss 1, Pp 1-14 (2020) |
| ISSN: | 2399-3642 |
| Popis: | Recent high-throughput approaches have revealed a vast number of transcripts with unknown functions. Many of these transcripts are long noncoding RNAs (lncRNAs), and intergenic region-derived lncRNAs are classified as long intergenic noncoding RNAs (lincRNAs). Although Myosin heavy chain 6 (Myh6) encoding primary contractile protein is down-regulated in stressed hearts, the underlying mechanisms are not fully clarified especially in terms of lincRNAs. Here, we screen upregulated lincRNAs in pressure overloaded hearts and identify a muscle-abundant lincRNA termed Lionheart. Compared with controls, deletion of the Lionheart in mice leads to decreased systolic function and a reduction in MYH6 protein levels following pressure overload. We reveal decreased MYH6 results from an interaction between Lionheart and Purine-rich element-binding protein A after pressure overload. Furthermore, human LIONHEART levels in left ventricular biopsy specimens positively correlate with cardiac systolic function. Our results demonstrate Lionheart plays a pivotal role in cardiac remodeling via regulation of MYH6. Kuwabara et al. identify a novel long intergenic noncoding RNA (lincRNA), termed Lionheart, upregulated in pressure overloaded hearts in mice. Deleting this gene results in decreased systolic function and reduction in MYH6 protein levels following pressure overload. They demonstrate that Lionheart interacts with PURA, preventing its binding to the promoter region of Myh6 locus, leading to reduced MYH6 protein expression. |
| Databáze: | OpenAIRE |
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