bims-micpro 2023-02-19 papers

Bio Protoc. 2023 Jan 05. 13(1): e4585

BONCAT-based Profiling of Nascent Small and Alternative Open Reading Frame-encoded Proteins.

Xiongwen Cao, Yanran Chen, Alexandra Khitun, Sarah A Slavoff.

RIBO-seq and proteogenomics have revealed that mammalian genomes harbor thousands of unannotated small and alternative open reading frames (smORFs, <100 amino acids, and alt-ORFs, >100 amino acids, respectively). Several dozen mammalian smORF-encoded proteins (SEPs) and alt-ORF-encoded proteins (alt-proteins) have been shown to play important biological roles, while the overwhelming majority of smORFs and alt-ORFs remain uncharacterized, particularly at the molecular level. Functional proteomics has the potential to reveal key properties of unannotated SEPs and alt-proteins in high throughput, and an approach to identify SEPs and alt-proteins undergoing regulated synthesis should be of broad utility. Here, we introduce a chemoproteomic pipeline based on bio-orthogonal non-canonical amino acid tagging (BONCAT) (Dieterich et al., 2006) to profile nascent SEPs and alt-proteins in human cells. This approach is able to identify cellular stress-induced and cell-cycle regulated SEPs and alt-proteins in cells. Graphical abstract Schematic overview of BONCAT-based chemoproteomic profiling of nascent, unannotated small and alternative open reading frame-encoded proteins (SEPs and alt-proteins).

Keywords: Alternative protein (alt-protein); Chemoproteomics; Micropeptide; Microprotein; Protein translation; Proteomics; Small open reading frame (smORF); Unnatural amino acid

DOI: https://doi.org/10.21769/BioProtoc.4585

Biophys J. 2023 Feb 10. pii: S0006-3495(22)03715-8. [Epub ahead of print]122(3S1): 527a

The mechanism of dwarf open reading frame (DWORF) activation of the sarcoplasmic reticulum calcium pump SERCA.

M'Lynn Fisher, Elisa Bovo, Rodrigo Aguayo-Ortiz, Ellen E Cho, Marsha P Pribadi, Michael P Dalton, Nishadh Rathod, M Joanne Lemieux, L Michel Espinoza-Fonseca, Seth L Robia, Aleksey V Zima, Howard S Young.

DOI: https://doi.org/10.1016/j.bpj.2022.11.2799

Cell Death Dis. 2023 Feb 15. 14(2): 126

A lncRNA-encoded mitochondrial micropeptide exacerbates microglia-mediated neuroinflammation in retinal ischemia/reperfusion injury.

Xintong Zheng, Mingwei Wang, Shuting Liu, Haiqiao Chen, Yifei Li, Fa Yuan, Ludong Yang, Suo Qiu, Hongwei Wang, Zhi Xie, Mengqing Xiang.

As a common pathology of many ocular disorders such as diabetic retinopathy and glaucoma, retinal ischemia/reperfusion (IR) triggers inflammation and microglia activation that lead to irreversible retinal damage. The detailed molecular mechanism underlying retinal IR injury, however, remains poorly understood at present. Here we report the bioinformatic identification of a lncRNA 1810058I24Rik (181-Rik) that was shown to encode a mitochondrion-located micropeptide Stmp1. Its deficiency in mice protected retinal ganglion cells from retinal IR injury by attenuating the activation of microglia and the Nlrp3 inflammasome pathway. Moreover, its genetic knockout in mice or knockdown in primary microglia promoted mitochondrial fusion, impaired mitochondrial membrane potential, and reactive oxygen species (ROS) production, diminished aerobic glycolysis, and ameliorated inflammation. It appears that 181-Rik may trigger the Nlrp3 inflammasome activation by controlling mitochondrial functions through inhibiting expression of the metabolic sensor uncoupling protein 2 (Ucp2) and activating expression of the Ca2+ sensors S100a8/a9. Together, our findings shed new light on the molecular pathogenesis of retinal IR injury and may provide a fresh therapeutic target for IR-associated neurodegenerative diseases.

DOI: https://doi.org/10.1038/s41419-023-05617-2

Trends Genet. 2023 Feb 09. pii: S0168-9525(23)00025-2. [Epub ahead of print]

Newly evolved genes in the human lineage are functional.

Chris Papadopoulos, M Mar Albà.

Genes restricted to a given species or lineage are mysterious. Many emerged de novo from ancestral noncoding genomic regions rather than from pre-existing genes. A new study by Vakirlis and colleagues shows that, in humans, many of these are associated with phenotypic effects, accelerating our understanding of their functional importance.

Keywords: CRISPR-Cas9; de novo gene; microprotein; ribosome profiling

DOI: https://doi.org/10.1016/j.tig.2023.02.001