Molecular and functional characterization of the Drosophila melanogaster conserved smORFome

Justin A. Bosch; Nathan Keith; Felipe Escobedo; William W. Fisher; James Thai LaGraff; Jorden Rabasco; Kenneth H. Wan; Richard Weiszmann; Yanhui Hu; Shu Kondo; James B. Brown; Norbert Perrimon; Susan E. Celniker

Cell Reports (Nov 2023)

Molecular and functional characterization of the Drosophila melanogaster conserved smORFome

Justin A. Bosch,
Nathan Keith,
Felipe Escobedo,
William W. Fisher,
James Thai LaGraff,
Jorden Rabasco,
Kenneth H. Wan,
Richard Weiszmann,
Yanhui Hu,
Shu Kondo,
James B. Brown,
Norbert Perrimon,
Susan E. Celniker

Affiliations

Justin A. Bosch: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
Nathan Keith: Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Felipe Escobedo: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
William W. Fisher: Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
James Thai LaGraff: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
Jorden Rabasco: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
Kenneth H. Wan: Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Richard Weiszmann: Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Yanhui Hu: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
Shu Kondo: Laboratory of Invertebrate Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
James B. Brown: Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Corresponding author
Norbert Perrimon: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA; Corresponding author
Susan E. Celniker: Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 11
p. 113311

Abstract

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Summary: Short polypeptides encoded by small open reading frames (smORFs) are ubiquitously found in eukaryotic genomes and are important regulators of physiology, development, and mitochondrial processes. Here, we focus on a subset of 298 smORFs that are evolutionarily conserved between Drosophila melanogaster and humans. Many of these smORFs are conserved broadly in the bilaterian lineage, and ∼182 are conserved in plants. We observe remarkably heterogeneous spatial and temporal expression patterns of smORF transcripts—indicating wide-spread tissue-specific and stage-specific mitochondrial architectures. In addition, an analysis of annotated functional domains reveals a predicted enrichment of smORF polypeptides localizing to mitochondria. We conduct an embryonic ribosome profiling experiment and find support for translation of 137 of these smORFs during embryogenesis. We further embark on functional characterization using CRISPR knockout/activation, RNAi knockdown, and cDNA overexpression, revealing diverse phenotypes. This study underscores the importance of identifying smORF function in disease and phenotypic diversity.

CP: Genomics

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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