bims-micpro 2024-09-08 papers

Issue of 2024‒09‒08
three papers selected by
Thomas Farid Martínez, University of California, Irvine

Funct Integr Genomics. 2024 Sep 03. 24(5): 152

Microproteins unveiling new dimensions in cancer.

S Daisy Precilla, Indrani Biswas, T S Anitha, B Agieshkumar.

In the complex landscape of cancer biology, the discovery of microproteins has triggered a paradigm shift, thereby, challenging the conventional conceptions of gene regulation. Though overlooked for years, these entities encoded by the small open reading frames (100-150 codons), have a significant impact on various cellular processes. As precision medicine pioneers delve deeper into the genome and proteome, microproteins have come into the limelight. Typically characterized by a single protein domain that directly binds to the target protein complex and regulates their assembly, these microproteins have been shown to play a key role in fundamental biological processes such as RNA processing, DNA repair, and metabolism regulation. Techniques for identification and characterization, such as ribosome profiling and proteogenomic approaches, have unraveled unique mechanisms by which these microproteins regulate cell signaling or pathological processes in most diseases including cancer. However, the functional relevance of these microproteins in cancer remains unclear. In this context, the current review aims to "rethink the essence of these genes" and explore "how these hidden players-microproteins orchestrate the signaling cascades of cancer, both as accelerators and brakes.".

Keywords: Apoptosis; Cancer; Microproteins; Signaling pathways; Small open reading frames

DOI: https://doi.org/10.1007/s10142-024-01426-8

Nat Commun. 2024 Aug 31. 15(1): 7563

A catalog of small proteins from the global microbiome.

Yiqian Duan, Célio Dias Santos-Júnior, Thomas Sebastian Schmidt, Anthony Fullam, Breno L S de Almeida, Chengkai Zhu, Michael Kuhn, Xing-Ming Zhao, Peer Bork, Luis Pedro Coelho.

Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we construct a global microbial smORFs catalog (GMSC) derived from 63,410 publicly available metagenomes across 75 distinct habitats and 87,920 high-quality isolate genomes. GMSC contains 965 million non-redundant smORFs with comprehensive annotations. We find that archaea harbor more smORFs proportionally than bacteria. We moreover provide a tool called GMSC-mapper to identify and annotate small proteins from microbial (meta)genomes. Overall, this publicly-available resource demonstrates the immense and underexplored diversity of small proteins.

DOI: https://doi.org/10.1038/s41467-024-51894-6

Commun Biol. 2024 Sep 04. 7(1): 1083

Differential effects of 40S ribosome recycling factors on reinitiation at regulatory uORFs in GCN4 mRNA are not dictated by their roles in bulk 40S recycling.

Kristína Jendruchová, Swati Gaikwad, Kristýna Poncová, Stanislava Gunišová, Leoš Shivaya Valášek, Alan G Hinnebusch.

Recycling of 40S ribosomal subunits following translation termination, entailing release of deacylated tRNA and dissociation of the empty 40S from mRNA, involves yeast Tma20/Tma22 heterodimer and Tma64, counterparts of mammalian MCTS1/DENR and eIF2D. MCTS1/DENR enhance reinitiation (REI) at short upstream open reading frames (uORFs) harboring penultimate codons that confer heightened dependence on these factors in bulk 40S recycling. Tma factors, by contrast, inhibited REI at particular uORFs in extracts; however, their roles at regulatory uORFs in vivo were unknown. We examined effects of eliminating Tma proteins on REI at regulatory uORFs mediating translational control of GCN4 optimized for either promoting (uORF1) or preventing (uORF4) REI. We found that the Tma proteins generally impede REI at native uORF4 and its variants equipped with various penultimate codons regardless of their Tma-dependence in bulk recycling. The Tma factors have no effect on REI at native uORF1 and equipping it with Tma-hyperdependent penultimate codons generally did not confer Tma-dependent REI; nor did converting the uORFs to AUG-stop elements. Thus, effects of the Tma proteins vary depending on the REI potential of the uORF and penultimate codon, but unlike in mammals, are not principally dictated by the Tma-dependence of the codon in bulk 40S recycling.

DOI: https://doi.org/10.1038/s42003-024-06761-x