mascRNA is a small cytoplasmic RNA derived from the lncRNA MALAT1. After being processed by the tRNA processing enzymes RNase P and RNase Z, mascRNA undergoes CCA addition like tRNAs and folds into a tRNA-like cloverleaf structure. While MALAT1 functions in multiple cellular processes, the role of mascRNA was largely unknown. Here, we show that mascRNA binds directly to the multi-tRNA synthetase complex (MSC) component glutaminyl-tRNA synthetase (QARS). mascRNA promotes global protein translation and cell proliferation by positively regulating QARS protein levels. Our results uncover a role of mascRNA that is independent of MALAT1, but could be part of the molecular mechanism of MALAT1's function in cancer, and provide a paradigm for understanding tRNA-like structures in mammalian cells.
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http://dx.doi.org/10.15252/embr.201949684 | DOI Listing |
Mol Immunol
February 2023
Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China; School of Life Science and Technology, Key Laboratory of Ministry of Education for Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu, China. Electronic address:
mascRNA (MALAT1-associated small cytoplasmic RNA) is a tRNA-like cytoplasmic small noncoding RNA whose function remains elusive. We previously revealed that this small RNA negatively regulates TLR4/2-triggered proinflammatory response while positively regulates TLR3-induced antiviral response. Here, we investigated whether and how mascRNA influences the stimulator of interferon genes (STING) signaling-triggered immune response.
View Article and Find Full Text PDFBiochem Biophys Res Commun
June 2022
Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China; School of Life Science and Technology, Key Laboratory of Ministry of Education for Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu, China. Electronic address:
Macrophages play a crucial role in the pathogenesis of rheumatoid arthritis (RA) and have been considered as a therapeutic target of this disease. Here we show that mascRNA, a tRNA-like cytoplasmic small noncoding RNA, promoted RIPK1-dependent apoptosis (RDA) in RAW267.4 macrophages in response to the TAK1 inhibitor 5Z-7-oxozeaenol (5Z-7) alone as well as in combination with TNF.
View Article and Find Full Text PDFJCI Insight
November 2021
School of Life Science and Technology, Key Laboratory of Ministry of Education for Developmental Genes and Human Disease.
MALAT1-associated small cytoplasmic RNA (mascRNA) is a highly conserved transfer RNA-like (tRNA-like) noncoding RNA whose function remains largely unknown. We show here that this small RNA molecule played a role in the stringent control of TLR-mediated innate immune responses. mascRNA inhibited activation of NF-κB and mitogen-activated protein kinase (MAPK) signaling and the production of inflammatory cytokines in macrophages stimulated with LPS, a TLR4 ligand.
View Article and Find Full Text PDFRNA
October 2021
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06536, USA.
Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a nuclear long noncoding RNA (lncRNA) that is highly overexpressed in many cancer tissues and plays important roles in tumor progression and metastasis. The MALAT1 primary transcript contains evolutionarily conserved structural elements in its 3'-terminal region: a triple helix forming element called element for nuclear expression (ENE) and a downstream tRNA-like structure called mascRNA. Instead of being polyadenylated, mature MALAT1 is generated by recognition and processing of the mascRNA by RNase P.
View Article and Find Full Text PDFCell Death Discov
May 2021
Vaccine Research Institute of Sun Yat-sen University, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
MALAT1-associated small cytoplasmic RNA (mascRNA) is a cytoplasmic tRNA-like small RNA derived from nucleus-located long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). While MALAT1 was extensively studied and was found to function in multiple cellular processes, including tumorigenesis and tumor progression, the role of mascRNA was largely unknown. Here we show that mascRNA is upregulated in multiple cancer cell lines and hepatocellular carcinoma (HCC) clinical samples.
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