bims-micpro 2025-08-03 papers

Nucleic Acids Res. 2025 Jul 19. pii: gkaf687. [Epub ahead of print]53(14):

Proteogenomics-enabled discovery of novel small open reading frame (sORF)-encoded polypeptides in human and mouse tissues.

Mei Yang, Yuting Xie, Lingshuo Wang, Irwin Jungreis, Tong Ou, Manolis Kellis, Jia Wang, Yafeng Zhu.

Small open reading frames (sORFs) encode an emerging class of functional proteins less than 100 amino acids in length. However, sORFs are incompletely characterized in mice and humans. The development of proteomics and Ribo-seq techniques has enabled the discovery of a number of sORF-encoded peptides (SEPs), but previous proteogenomics studies have been limited to a few cell lines or tissues. Given these limitations, a potentially vast number of sORFs remains to be discovered. We collected community-scale previously published proteomics data including one billion experimental spectra derived from a wide range of mouse and human tissues in order to identify novel sORFs and reveal the tissue expression status of novel and recently annotated sORF-encoded proteins. We have detected several novel sORFs in specific tissues, including a conserved protein-coding upstream overlapping ORF in HNRNPUL2 expressed in human lymphocytes, which may hold important biological functions. This work introduces a simple and efficient filtration strategy to detect novel sORFs. Our workflow will likely prove useful for future studies on sORFs in humans and other animals.

DOI: https://doi.org/10.1093/nar/gkaf687

Noncoding RNA Res. 2025 Dec;15 44-50

Overview of small proteins encoded by bacterial dual-function small RNAs.

Xia Cai, Hui Shan, Jiaojiao Wang, Jiaxin Qin, Huiling Gong, Jun Cai, Jin He.

Small RNAs (sRNAs) are widely used by bacteria to regulate diverse biological processes. Although they are generally considered "non-coding", some sRNAs (called dual-function sRNAs) have been found to encode small proteins, which are usually less than 50 amino acids in length and have long been overlooked due to significant challenges in their annotation and biochemical detection. However, in the past few decades, an increasing number of small proteins encoded by dual-function sRNAs have been reported. Previous reviews of dual-function sRNAs have mainly focused on their base-pairing nucleic acid functions, with less emphasis on the nature of their translated peptides, resulting in limited understanding of their full functional scope. This article reviews ten small proteins encoded by dual-function sRNAs and introduces their physiological functions, interacting protein partners, and the research methods used, aiming to provide new perspectives and directions for the study of small proteins and enhance understanding of bacterial regulatory mechanisms mediated by dual-function sRNAs.

Keywords: Biological function; Dual-function sRNA; Protein partner; Small protein

DOI: https://doi.org/10.1016/j.ncrna.2025.07.002

Cell Signal. 2025 Jul 29. pii: S0898-6568(25)00445-0. [Epub ahead of print] 112030

1110025M09Rik-encoded protein regulates adipogenic differentiation in murine bone marrow stromal cells.

Xinyu Wang, Shuanglin Du, Shuhan Xing, Endong Zhu, Jie Zhou, Baoli Wang, Hairui Yuan.

Bone marrow adipose tissue (BMAT) plays a pivotal role in skeletal health and metabolism, yet the molecular mechanisms governing the commitment of bone marrow stromal cells (BMSCs) to the adipocyte lineage remain incompletely understood. Here, we identified 1110025M09Rik, a locus previously annotated as a long non-coding RNA (lncRNA), which contains an open reading frame (ORF) encoding a functional protein essential for adipogenesis. Overexpression of 1110025M09Rik significantly enhanced adipogenic differentiation in both ST2 stromal cells and primary BMSCs. Conversely, the knockdown of 1110025M09Rik resulted in reduced lipid accumulation and decreased expression of adipocyte markers in these cells. In vivo, deletion of 1110025M09Rik led to decreased bone marrow fat deposition in middle-aged mice and impaired adipogenic capacity of BMSCs isolated from knockout mice. Mechanistically, loss of 1110025M09Rik resulted in upregulation of kininogen 2 (Kng2), which we identified as a negative regulator of adipocyte differentiation. Importantly, silencing Kng2 restored the adipogenic potential in 1110025M09Rik-knockdown cells. These findings establish 1110025M09Rik as a protein-coding gene that regulates BMAT development, providing novel insights into the molecular mechanisms of adipogenesis and highlighting potential therapeutic targets for skeletal and metabolic disorders.

Keywords: 1110025M09Rik; Adipocyte differentiation; Bone marrow adipose tissue; Bone marrow stromal cells; Novel protein

DOI: https://doi.org/10.1016/j.cellsig.2025.112030