bims-micpro 2022-05-08 papers

Issue of 2022‒05‒08
two papers selected by
Thomas Farid Martínez
University of California, Irvine

J Clin Invest. 2022 May 02. pii: e158449. [Epub ahead of print]132(9):

Mitochondria-derived peptides in aging and healthspan.

Brendan Miller, Su-Jeong Kim, Hiroshi Kumagai, Kelvin Yen, Pinchas Cohen.

The mechanisms that explain mitochondrial dysfunction in aging and healthspan continue to be studied, but one element has been unexplored: microproteins. Small open reading frames in circular mitochondria DNA can encode multiple microproteins, called mitochondria-derived peptides (MDPs). Currently, eight MDPs have been published: humanin, MOTS-c, and SHLPs 1-6. This Review describes recent advances in microprotein discovery with a focus on MDPs. It discusses what is currently known about MDPs in aging and how this new understanding could add to the way we understand age-related diseases including type 2 diabetes, cancer, and neurodegenerative diseases at the genomic, proteomic, and drug-development levels.

DOI: https://doi.org/10.1172/JCI158449

Nat Plants. 2022 May 02.

Noise reduction by upstream open reading frames.

Ho-Wei Wu, Erickson Fajiculay, Jing-Fen Wu, Ching-Cher Sanders Yan, Chao-Ping Hsu, Shu-Hsing Wu.

Gene expression is prone to burst production, making it a highly noisy process that requires additional controls. Upstream open reading frames (uORFs) are widely present in the 5' leader sequences of 30-50% of eukaryotic messenger RNAs1-3. The translation of uORFs can repress the translation efficiency of the downstream main coding sequences. Whether the low translation efficiency leads to a different variation, or noise, in gene expression has not been investigated, nor has the direct biological impact of uORF-repressed translation. Here we show that uORFs achieve low but precise protein production in plant cells, possibly by reducing the protein production rate. We also demonstrate that, by buffering a stable TIMING OF CAB EXPRESSION 1 (TOC1) protein production level, uORFs contribute to the robust operation of the plant circadian clock. Our results provide both an action model and the biological impact of uORFs in translational control to mitigate transcriptional noise for precise protein production.

DOI: https://doi.org/10.1038/s41477-022-01136-8