bims-micpro 2024-09-22 papers

NPJ Regen Med. 2024 Sep 19. 9(1): 23

Calorie restriction and rapamycin distinctly restore non-canonical ORF translation in the muscles of aging mice.

Nitish Mittal, Meric Ataman, Lionel Tintignac, Daniel J Ham, Lena Jörin, Alexander Schmidt, Michael Sinnreich, Markus A Ruegg, Mihaela Zavolan.

Loss of protein homeostasis is one of the hallmarks of aging. As such, interventions that restore proteostasis should slow down the aging process and improve healthspan. Two of the most broadly used anti-aging interventions that are effective in organisms from yeast to mammals are calorie restriction (CR) and rapamycin (RM) treatment. To identify the regulatory mechanisms by which these interventions improve the protein homeostasis, we carried out ribosome footprinting in the muscle of mice aged under standard conditions, or under long-term treatment with CR or RM. We found that the treatments distinctly impact the non-canonical translation, RM primarily remodeling the translation of upstream open reading frames (uORFs), while CR restores stop codon readthrough and the translation of downstream ORFs. Proteomics analysis revealed the expression of numerous non-canonical ORFs at the protein level. The corresponding peptides may provide entry points for therapies aiming to maintain muscle function and extend health span.

DOI: https://doi.org/10.1038/s41536-024-00369-9

Nat Commun. 2024 Sep 19. 15(1): 8219

Discovering the hidden function in fungal genomes.

Nicholas C Gervais, Rebecca S Shapiro.

New molecular technologies have helped unveil previously unexplored facets of the genome beyond the canonical proteome, including microproteins and short ORFs, products of alternative splicing, regulatory non-coding RNAs, as well as transposable elements, cis-regulatory DNA, and other highly repetitive regions of DNA. In this Review, we highlight what is known about this 'hidden genome' within the fungal kingdom. Using well-established model systems as a contextual framework, we describe key elements of this hidden genome in diverse fungal species, and explore how these factors perform critical functions in regulating fungal metabolism, stress tolerance, and pathogenesis. Finally, we discuss new technologies that may be adapted to further characterize the hidden genome in fungi.

DOI: https://doi.org/10.1038/s41467-024-52568-z

Pestic Biochem Physiol. 2024 Sep;pii: S0048-3575(24)00279-7. [Epub ahead of print]204 106046

Lnc557 promotes Bombyx mori nucleopolyhedrovirus replication by interacting with BmELAVL1 to enhance its stability and expression.

Su Lin, Zhen-Yu Shen, Meng-Dong Wang, Xue-Min Zhou, Tao Xu, Xin-Hao Jiao, Lu-Lai Wang, Xi-Jie Guo, Ping Wu.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen that threatens the growth and sustainability of the sericultural industry. Currently, accumulated studies showed that long non-coding RNAs (lncRNAs) play important roles in the genesis and progression of various viruses and host-pathogens interactions. However, the functions and regulatory mechanisms of lncRNAs in insect-virus interaction are still limited. In this study, transcriptome sequencing and ribosome profiling sequencing (Ribo-seq) were performed in the BmNPV-infected midgut and control tissue, and a total of 9 differentially expressed (DE) lncRNAs and 27 small ORFs (sORFs) with micropeptide coding potential were identified. Among them, lncRNA XR_001139971.3 (lnc557) is verified to be significantly up-regulated upon BmNPV infection and may have the potential to encode a small peptide (ORF-674). The subcellular localization experiment showed that lnc557 was expressed in the cytoplasm. Overexpression of lnc557 promotes BmNPV replication and vice versa. By combining RNA pull-down, mass spectrometry, protein truncation and RNA immunoprecipitation (RIP) assays, we confirmed that lnc557 can bind to the RRM-5 domain of BmELAVL1 protein. Subsequently, we found that lnc557 could promote the expression of BmELAVL1 by enhancing the stability of BmELAVL1. Further, enhancing the expression of BmELAVL1 can promote the proliferation of BmNPV, while knockdown shows the opposite effect. Our data suggest that lnc557-mediated BmELAVL1 expression enhancement could play a positive role in BmNPV replication, which will provide a new insight into the molecular mechanism of interaction between Bombyx mori and virus.

Keywords: BmNPV; Insect-pathogen interaction; RNA-protein interaction; lncRNA

DOI: https://doi.org/10.1016/j.pestbp.2024.106046