bims-micpro 2022-07-10 papers

Issue of 2022‒07‒10
two papers selected by
Thomas Farid Martínez
University of California, Irvine

Mol Cell Proteomics. 2022 Jul 01. pii: S1535-9476(22)00072-X. [Epub ahead of print] 100264

Limited evidence for protein products of non-coding transcripts in the HEK293T cellular cytosol.

Annelies Bogaert, Daria Fijalkowska, An Staes, Tessa Van de Steene, Hans Demol, Kris Gevaert.

Ribosome profiling has revealed translation outside of canonical coding sequences (CDSs) including translation of short upstream ORFs, long non-coding RNAs, overlapping ORFs, ORFs in UTRs or ORFs in alternative reading frames. Studies combining mass spectrometry, ribosome profiling and CRISPR-based screens showed that hundreds of ORFs derived from non-coding transcripts produce (micro)proteins, while other studies failed to find evidence for such types of non-canonical translation products. Here, we attempted to discover translation products from non-coding regions by strongly reducing the complexity of the sample prior to mass spectrometric analysis. We used an extended database as the search space and applied stringent filtering of the identified peptides to find evidence for novel translation events. We show that, theoretically our strategy facilitates the detection of translation events of transcripts from non-coding regions, but experimentally only find 19 peptides that might originate from such translation events. Finally, Virotrap based interactome analysis of two N-terminal proteoforms originating from non-coding regions finally showed the functional potential of these novel proteins.

DOI: https://doi.org/10.1016/j.mcpro.2022.100264

Prostate. 2022 Jul 05.

Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities.

Adela Ramirez-Torres, Allison L Reagan, Lauren E Howard, Emily Wiggins, Adriana C Vidal, Junxiang Wan, Brendan Miller, Stephen J Freedland, Pinchas Cohen.

INTRODUCTION: The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer (PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PC risk by race.METHODS: Plasma SHLP2, humanin, and MOTS-c were measured in 198 men (50/49 EAM/AAM cases; 50/49 EAM/AAM controls) undergoing biopsy. Logistic and multinomial regression models tested associations between each MDP and PC diagnosis, low-grade (grade group, GG1) and high-grade (GG2-5). Models were adjusted for age, body mass index, digital rectal examination, and prostate specific antigen (PSA). We tested interactions between MDPs and race.
RESULTS: Among controls, humanin was similar by race (p = 0.60), but both SHLP2 (p = 0.007) and MOTS-c (p = 0.026) were lower in AAM controls versus EAM controls. Among EAM, higher MDP values were associated with lower PC risk (all p ≤ 0.001), with null associations in AAM (all p-interactions ≤ 0.01). Similarly, higher MDP expression was associated with decreased risk of low- and high-grade PC in EAM (all p ≤ 0.005) with null associations in AAM.
CONCLUSIONS: Higher MDP levels were associated with lower PC risk in EAM but not AAM. Generally, AAM controls had lower MDP levels. These data support MDPs and mitochondrial dysfunction in PC, suggesting greater dysfunction in AAM may contribute to excess PC risk. Future larger studies are needed to confirm these results.

Keywords: disparities; mitochondrial dysfunction; mitochondrial genome; mitochondrial-derived peptides (MDPs); prostate cancer

DOI: https://doi.org/10.1002/pros.24398