2. Academic Validation
  3. Labeling of heterochronic ribosomes reveals C1ORF109 and SPATA5 control a late step in human ribosome assembly

Labeling of heterochronic ribosomes reveals C1ORF109 and SPATA5 control a late step in human ribosome assembly

  • Cell Rep. 2022 Mar 29;38(13):110597. doi: 10.1016/j.celrep.2022.110597.
Chunyang Ni 1,  Daniel A Schmitz 1,  Jeon Lee 2,  Krzysztof Pawłowski 1,  Jun Wu 3,  Michael Buszczak 4
Affiliations

Affiliations

  • 1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
  • 2 Lyda Hill-Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9365, USA.
  • 3 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
  • 4 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Electronic address: michael.buszczak@utsouthwestern.edu.
PMID: 35354024 DOI: 10.1016/j.celrep.2022.110597
Abstract

Although features of ribosome assembly are shared between species, our understanding of the diversity, complexity, dynamics, and regulation of ribosome production in multicellular organisms remains incomplete. To gain insights into ribosome biogenesis in human cells, we perform a genome-wide loss-of-function screen combined with differential labeling of pre-existing and newly assembled ribosomes. These efforts identify two functionally uncharacterized genes, C1orf109 and SPATA5. We provide evidence that these factors, together with CINP and SPATA5L1, control a late step of human pre-60S maturation in the cytoplasm. Loss of either C1orf109 or SPATA5 impairs global protein synthesis. These results link ribosome assembly with neurodevelopmental disorders associated with recessive SPATA5 mutations. Based on these findings, we propose that the expanded repertoire of ribosome biogenesis factors likely enables multicellular organisms to coordinate multiple steps of ribosome production in response to different developmental and environmental stimuli.

Keywords

C1ORF109; CINP; CP: Molecular biology; RSL24D1; Ribosome biogenesis; SPATA5; SPATA5L1; mRNA translation; microcephaly.

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