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Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes

ABSTRACT: Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes

PROVIDER: PRJNA1074781 | ENA |

REPOSITORIES: ENA

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Multiprotein bridging factor 1 is required for robust activation of the integrated stress response on collided ribosomes

Project description:The multiprotein bridging factor 1 (Mbf1) proteins are a family of conserved eukaryotic proteins thought to mediate the activity of stress-induced transcription factors. In yeast, Mbf1 has been proposed to function in the integrated stress response (ISR) by mediating an interaction between the basal transcription machinery and the process’s key effector Gcn4. Curiously, mounting recent evidence has strongly suggested that the factor and its human homologue to be recruited to collided ribosomes, the very signal newly recognized to activate the ISR. Here we provide data that connect these otherwise supposedly disparate functions of the factor. Our findings revealed that Mbf1 functions as a core factor in the ISR process, responding early to stress and mediating the activation of Gcn2. We further show that the factor serves no role as a transcriptional coactivator of Gcn4; instead, it is required for optimal stress-induced eIF2a phosphorylation and downstream de-repression of GCN4 translation. Detailed mutational and biochemical analysis, together with a cryo-EM structure of the factor bound to collided ribosomes, showed that Mbf1’s activity in the ISR is enabled through its interaction with ribosomes. Collectively, our data resolve an important question about how Mbf1 factors function in signaling by acting as sensors of stress-induced ribosomes collisions, and not as coactivators of the effector proteins as widely accepted in the field.

2024-12-18 | GSE255383 | GEO

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

Project description:Although several ribosomal protein (RP) 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 (RPL3L-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-ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-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 new insight into the mechanisms and physiological relevance of tissue-specific translational regulation.

2023-03-15 | GSE203072 | GEO

Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes

Project description:Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes

| PRJNA655414 | ENA

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

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Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [STAMP_pacbio]

Project description:Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [STAMP_pacbio]

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Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [NP]

Project description:Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [NP]

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Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [tia1_eclip]

Project description:Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [tia1_eclip]

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Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [STAMP_new_eclip]

Project description:Robust single-cell discovery of RNA targets of RNA binding proteins and ribosomes [STAMP_new_eclip]

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Sen1 is required for robust RNA Polymerase III transcription termination

Project description:Sen1 is required for robust RNA Polymerase III transcription termination

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Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis

Project description:Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis

| PRJNA623379 | ENA

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