bims-micpro 2023-11-19 papers

Issue of 2023‒11‒19
three papers selected by
Thomas Farid Martínez, University of California, Irvine

Nucleic Acids Res. 2023 Nov 13. pii: gkad1050. [Epub ahead of print]

OpenProt 2.0 builds a path to the functional characterization of alternative proteins.

Sébastien Leblanc, Feriel Yala, Nicolas Provencher, Jean-François Lucier, Maxime Levesque, Xavier Lapointe, Jean-Francois Jacques, Isabelle Fournier, Michel Salzet, Aïda Ouangraoua, Michelle S Scott, François-Michel Boisvert, Marie A Brunet, Xavier Roucou.

The OpenProt proteogenomic resource (https:////www.openprot.org//) provides users with a complete and freely accessible set of non-canonical or alternative open reading frames (AltORFs) within the transcriptome of various species, as well as functional annotations of the corresponding protein sequences not found in standard databases. Enhancements in this update are largely the result of user feedback and include the prediction of structure, subcellular localization, and intrinsic disorder, using cutting-edge algorithms based on machine learning techniques. The mass spectrometry pipeline now integrates a machine learning-based peptide rescoring method to improve peptide identification. We continue to help users explore this cryptic proteome by providing OpenCustomDB, a tool that enables users to build their own customized protein databases, and OpenVar, a genomic annotator including genetic variants within AltORFs and protein sequences. A new interface improves the visualization of all functional annotations, including a spectral viewer and the prediction of multicoding genes. All data on OpenProt are freely available and downloadable. Overall, OpenProt continues to establish itself as an important resource for the exploration and study of new proteins.

DOI: https://doi.org/10.1093/nar/gkad1050

aBIOTECH. 2023 Sep;4(3): 238-256

Shining in the dark: the big world of small peptides in plants.

Yan-Zhao Feng, Qing-Feng Zhu, Jiao Xue, Pei Chen, Yang Yu.

Small peptides represent a subset of dark matter in plant proteomes. Through differential expression patterns and modes of action, small peptides act as important regulators of plant growth and development. Over the past 20 years, many small peptides have been identified due to technical advances in genome sequencing, bioinformatics, and chemical biology. In this article, we summarize the classification of plant small peptides and experimental strategies used to identify them as well as their potential use in agronomic breeding. We review the biological functions and molecular mechanisms of small peptides in plants, discuss current problems in small peptide research and highlight future research directions in this field. Our review provides crucial insight into small peptides in plants and will contribute to a better understanding of their potential roles in biotechnology and agriculture.

Keywords: Biological function; Crop improvement; Regulatory mechanism; Small peptide

DOI: https://doi.org/10.1007/s42994-023-00100-0

Circ Res. 2023 Nov 13.

DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters.

Nienke M Stege, Tim R Eijgenraam, Vivian Oliveira Nunes Teixeira, Anna M Feringa, Elisabeth M Schouten, Diederik W D Kuster, Jolanda van der Velden, Anouk H G Wolters, Ben N G Giepmans, Catherine A Makarewich, Rhonda Bassel-Duby, Eric N Olson, Rudolf A de Boer, Herman H W Silljé.

BACKGROUND: The p.Arg14del variant of the PLN (phospholamban) gene causes cardiomyopathy, leading to severe heart failure. Calcium handling defects and perinuclear PLN aggregation have both been suggested as pathological drivers of this disease. Dwarf open reading frame (DWORF) has been shown to counteract PLN regulatory calcium handling function in the sarco/endoplasmic reticulum (S/ER). Here, we investigated the potential disease-modulating action of DWORF in this cardiomyopathy and its effects on calcium handling and PLN aggregation.METHODS: We studied a PLN-R14del mouse model, which develops cardiomyopathy with similar characteristics as human patients, and explored whether cardiac DWORF overexpression could delay cardiac deterioration. To this end, R14Δ/Δ (homozygous PLN-R14del) mice carrying the DWORF transgene (R14Δ/ΔDWORFTg [R14Δ/Δ mice with a copy of the DWORF transgene]) were used.
RESULTS: DWORF expression was suppressed in hearts of R14Δ/Δ mice with severe heart failure. Restoration of DWORF expression in R14Δ/Δ mice delayed cardiac fibrosis and heart failure and increased life span >2-fold (from 8 to 18 weeks). DWORF accelerated sarcoplasmic reticulum calcium reuptake and relaxation in isolated cardiomyocytes with wild-type PLN, but in R14Δ/Δ cardiomyocytes, sarcoplasmic reticulum calcium reuptake and relaxation were already enhanced, and no differences were detected between R14Δ/Δ and R14Δ/ΔDWORFTg. Rather, DWORF overexpression delayed the appearance and formation of large pathogenic perinuclear PLN clusters. Careful examination revealed colocalization of sarcoplasmic reticulum markers with these PLN clusters in both R14Δ/Δ mice and human p.Arg14del PLN heart tissue, and hence these previously termed aggregates are comprised of abnormal organized S/ER. This abnormal S/ER organization in PLN-R14del cardiomyopathy contributes to cardiomyocyte cell loss and replacement fibrosis, consequently resulting in cardiac dysfunction.
CONCLUSIONS: Disorganized S/ER is a major characteristic of PLN-R14del cardiomyopathy in humans and mice and results in cardiomyocyte death. DWORF overexpression delayed PLN-R14del cardiomyopathy progression and extended life span in R14Δ/Δ mice, by reducing abnormal S/ER clusters.

Keywords: cardiomyopathies; fibrosis; longevity; sarcoplasmic reticulum; transgenes

DOI: https://doi.org/10.1161/CIRCRESAHA.123.323304