title: Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18.
abstract: In response to stress, cells attenuate global protein synthesis but permit efficient translation of mRNAs encoding heat-shock proteins (HSPs). Although decades have passed since the first description of the heat-shock response, how cells achieve translational control of HSP synthesis remains enigmatic. Here we report an unexpected role for mitochondrial ribosomal protein L18 (MRPL18) in the mammalian cytosolic stress response. MRPL18 bears a downstream CUG start codon and generates a cytosolic isoform in a stress-dependent manner. Cytosolic MRPL18 incorporates into the 80S ribosome and facilitates ribosome engagement on mRNAs selected for translation during stress. MRPL18 knockdown has minimal effects on mitochondrial function but substantially dampens cytosolic HSP expression at the level of translation. Our results uncover a hitherto-uncharacterized stress-adaptation mechanism in mammalian cells, which involves formation of a 'hybrid' ribosome responsible for translational regulation during the cytosolic stress response.
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
authors: Xingqian
authors: X
authors: Zhang
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
authors: Xiangwei
authors: X
authors: Gao
authors: 1] Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA. [2] Graduate Field of Nutritional Sciences, Cornell University, Ithaca, New York, USA.
authors: Ryan Alex
authors: RA
authors: Coots
authors: Graduate Field of Genetics, Genomics and Development, Cornell University, Ithaca, New York, USA.
authors: Crystal S
authors: CS
authors: Conn
authors: Graduate Field of Genetics, Genomics and Development, Cornell University, Ithaca, New York, USA.
authors: Botao
authors: B
authors: Liu
authors: 1] Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA. [2] Graduate Field of Nutritional Sciences, Cornell University, Ithaca, New York, USA. [3] Graduate Field of Genetics, Genomics and Development, Cornell University, Ithaca, New York, USA.
authors: Shu-Bing
authors: SB
authors: Qian
mesh_terms: D045744:Cell Line, Tumor; D018387:Codon, Initiator / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D018869:Heat-Shock Response / Q000235:genetics; D006801:Humans; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics; D013312:Stress, Physiological / Q000502:physiology*; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D018387:Codon, Initiator; D006360:Heat-Shock Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; C029609:ribosomal protein L18; C583541:EIF2AK1 protein, human; D019892:eIF-2 Kinase