bims-micpro 2024-05-26 papers

NAR Cancer. 2024 Jun;6(2): zcae023

Upstream open reading frames: new players in the landscape of cancer gene regulation.

The translation of RNA by ribosomes represents a central biological process and one of the most dysregulated processes in cancer. While translation is traditionally thought to occur exclusively in the protein-coding regions of messenger RNAs (mRNAs), recent transcriptome-wide approaches have shown abundant ribosome activity across diverse stretches of RNA transcripts. The most common type of this kind of ribosome activity occurs in gene leader sequences, also known as 5' untranslated regions (UTRs) of the mRNA, that precede the main coding sequence. Translation of these upstream open reading frames (uORFs) is now known to occur in upwards of 25% of all protein-coding genes. With diverse functions from RNA regulation to microprotein generation, uORFs are rapidly igniting a new arena of cancer biology, where they are linked to cancer genetics, cancer signaling, and tumor-immune interactions. This review focuses on the contributions of uORFs and their associated 5'UTR sequences to cancer biology.

DOI: https://doi.org/10.1093/narcan/zcae023

Noncoding RNA Res. 2024 Sep;9(3): 964-969

Biochemical targets of the micropeptides encoded by lncRNAs.

Bi-Ying Wang, Qi Gao, Yan Sun, Xiao-Bo Qiu.

Long non-coding RNAs (lncRNAs) are a group of transcripts longer than 200 nucleotides, which play important roles in regulating various cellular activities by the action of the RNA itself. However, about 40% of lncRNAs in human cells are potentially translated into micropeptides (also referred to as microproteins) usually shorter than 100 amino acids. Thus, these lncRNAs may function by both RNAs directly and their encoded micropeptides. The micropeptides encoded by lncRNAs may regulate transcription, translation, protein phosphorylation or degradation, or subcellular membrane functions. This review attempts to summarize the biochemical targets of the micropeptides-encoded by lncRNAs, which function by both RNAs and micropeptides, and discuss their associations with various diseases and their potentials as drug targets.

Keywords: Biochemical target; LncRNA; Micropeptide; Microprotein

DOI: https://doi.org/10.1016/j.ncrna.2024.04.005

Annu Rev Microbiol. 2024 May 21.

Large Roles of Small Proteins.

Aisha T Burton, Rilee Zeinert, Gisela Storz.

Bacterial proteins of ≤50 amino acids, denoted small proteins or microproteins, have been traditionally understudied and overlooked, as standard computational, biochemical, and genetic approaches often do not detect proteins of this size. However, with the realization that small proteins are stably expressed and have important cellular roles, there has been increased identification of small proteins in bacteria and eukaryotes. Gradually, the functions of a few of these small proteins are being elucidated. Many interact with larger protein products to modulate their subcellular localization, stabilities, or activities. Here, we provide an overview of these diverse functions in bacteria, highlighting generalities among bacterial small proteins and similarly sized proteins in eukaryotic organisms and discussing questions for future research.

DOI: https://doi.org/10.1146/annurev-micro-112723-083001

Antioxidants (Basel). 2024 May 17. pii: 613. [Epub ahead of print]13(5):

The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism.

Yanli Zhang, Jianfeng Huang, Yaru Zhang, Fengjuan Jiang, Shengpeng Li, Shuai He, Jiaojiao Sun, Dan Chen, Ying Tong, Qingfeng Pang, Yaxian Wu.

Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack of effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating mitochondrial injury. C57BL/6 mice were exposed to 20 Gy of lung irradiation (IR) and received daily intraperitoneal injections of MOTS-c for 2 weeks. MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by radiation. Meanwhile, MOTS-c reversed the apoptosis and mitochondrial damage of alveolar epithelial cells in RP mice. Furthermore, MOTS-c significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells and primary mouse lung epithelial cells. Mechanistically, MOTS-c increased the nuclear factor erythroid 2-related factor (Nrf2) level and promoted its nuclear translocation. Notably, Nrf2 deficiency abolished the protective function of MOTS-c in mice with RP. In conclusion, MOTS-c alleviates RP by protecting mitochondrial function through an Nrf2-dependent mechanism, indicating that MOTS-c may be a novel potential protective agent against RP.

Keywords: MOTS-c; Nrf2; epithelial cells; mitochondrial function; radiation pneumonitis

DOI: https://doi.org/10.3390/antiox13050613