Small Proteins; Big Questions
Overview
Authors
Affiliations
In recent years, there has been increased appreciation that a whole category of proteins, small proteins of around 50 amino acids or fewer in length, has been missed by annotation as well as by genetic and biochemical assays. With the increased recognition that small proteins are stable within cells and have regulatory functions, there has been intensified study of these proteins. As a result, important questions about small proteins in bacteria and archaea are coming to the fore. Here, we give an overview of these questions, the initial answers, and the approaches needed to address these questions more fully. More detailed discussions of how small proteins can be identified by ribosome profiling and mass spectrometry approaches are provided by two accompanying reviews (N. Vazquez-Laslop, C. M. Sharma, A. S. Mankin, and A. R. Buskirk, J Bacteriol 204:e00294-21, 2022, https://doi.org/10.1128/JB.00294-21; C. H. Ahrens, J. T. Wade, M. M. Champion, and J. D. Langer, J Bacteriol 204:e00353-21, 2022, https://doi.org/10.1128/JB.00353-21). We are excited by the prospects of new insights and possible therapeutic approaches coming from this emerging field.
The hidden bacterial microproteome.
Fesenko I, Sahakyan H, Dhyani R, Shabalina S, Storz G, Koonin E Mol Cell. 2025; 85(5):1024-1041.e6.
PMID: 39978337 PMC: 11890958. DOI: 10.1016/j.molcel.2025.01.025.
sORFdb - a database for sORFs, small proteins, and small protein families in bacteria.
Hahnfeld J, Schwengers O, Jelonek L, Diedrich S, Cemic F, Goesmann A BMC Genomics. 2025; 26(1):110.
PMID: 39910485 PMC: 11796252. DOI: 10.1186/s12864-025-11301-w.
Functional characterization of the DUF1127-containing small protein YjiS of Typhimurium.
Venturini E, Maass S, Bischler T, Becher D, Vogel J, Westermann A Microlife. 2025; 6:uqae026.
PMID: 39790481 PMC: 11707872. DOI: 10.1093/femsml/uqae026.
TSS-Captur: a user-friendly pipeline for characterizing unclassified RNA transcripts.
Witte Paz M, Vogel T, Nieselt K NAR Genom Bioinform. 2024; 6(4):lqae168.
PMID: 39703424 PMC: 11655288. DOI: 10.1093/nargab/lqae168.
Yang Y, Yan J, Olson R, Jiang X bioRxiv. 2024; .
PMID: 39372729 PMC: 11451748. DOI: 10.1101/2024.08.19.608685.