RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function

• Published in: Nature communications Vol. 14; no. 1; p. 2131
• Main Authors: Shiraishi, Chisa, Matsumoto, Akinobu, Ichihara, Kazuya, Yamamoto, Taishi, Yokoyama, Takeshi, Mizoo, Taisuke, Hatano, Atsushi, Matsumoto, Masaki, Tanaka, Yoshikazu, Matsuura-Suzuki, Eriko, Iwasaki, Shintaro, Matsushima, Shouji, Tsutsui, Hiroyuki, Nakayama, Keiichi I.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 38; 38/91; 42; 45; 45/41; 631/337/574/1789; 631/45/612/1249; 692/699/75/230; 82/58; Animals; Cardiac muscle; Cardiomyopathy; Codons; Dilated cardiomyopathy; Dynamics; Elongation; Humanities and Social Sciences; Male; Mice; multidisciplinary; Muscle contraction; Muscle, Skeletal - metabolism; Muscles; Muscular function; Musculoskeletal system; Myoblasts; Peptide Chain Elongation, Translational; Protein Biosynthesis; Proteins; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; Ribosomes; Ribosomes - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Skeletal muscle; Transcriptomes; Translation elongation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37838-6

Although several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation. RPL3L is a paralog of the ribosomal protein RPL3 and specifically expressed in heart and skeletal muscle. Here, the authors show that RPL3L-containing ribosomes regulate translation elongation dynamics especially for the transcripts related to cardiac muscle contraction.