bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2023–04–09
two papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in renal cell carcinoma.
  2. Ribosome footprint profiling enables elucidating the systemic regulation of fatty acid accumulation in Acer truncatum.
  1. EMBO Rep. 2023 Apr 03. e56282
    LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in renal cell carcinoma.
    Kun Meng, Shaohua Lu, Yu-Ying Li, Li-Ling Hu, Jing Zhang, Yun Cao, Yang Wang, Chris Zhiyi Zhang, Qing-Yu He.
      Human microproteins encoded by long non-coding RNAs (lncRNA) have been increasingly discovered, however, complete functional characterization of these emerging proteins is scattered. Here, we show that LINC00493-encoded SMIM26, an understudied microprotein localized in mitochondria, is tendentiously downregulated in clear cell renal cell carcinoma (ccRCC) and correlated with poor overall survival. LINC00493 is recognized by RNA-binding protein PABPC4 and transferred to ribosomes for translation of a 95-amino-acid protein SMIM26. SMIM26, but not LINC00493, suppresses ccRCC growth and metastatic lung colonization by interacting with acylglycerol kinase (AGK) and glutathione transport regulator SLC25A11 via its N-terminus. This interaction increases the mitochondrial localization of AGK and subsequently inhibits AGK-mediated AKT phosphorylation. Moreover, the formation of the SMIM26-AGK-SCL25A11 complex maintains mitochondrial glutathione import and respiratory efficiency, which is abrogated by AGK overexpression or SLC25A11 knockdown. This study functionally characterizes the LINC00493-encoded microprotein SMIM26 and establishes its anti-metastatic role in ccRCC, and therefore illuminates the importance of hidden proteins in human cancers.
    Keywords:  SMIM26; clear cell renal cell carcinoma; hidden proteins; metastasis; microproteins
    DOI:  https://doi.org/10.15252/embr.202256282
  2. BMC Biol. 2023 Apr 03. 21(1): 68
    Ribosome footprint profiling enables elucidating the systemic regulation of fatty acid accumulation in Acer truncatum.
    Qiuyue Ma, Yuxiao Wang, Shushun Li, Jing Wen, Lu Zhu, Kunyuan Yan, Yiming Du, Shuxian Li, Liping Yan, Zhijun Xie, Yunzhou Lyu, Fei Shen, Qianzhong Li.
       BACKGROUND: The accumulation of fatty acids in plants covers a wide range of functions in plant physiology and thereby affects adaptations and characteristics of species. As the famous woody oilseed crop, Acer truncatum accumulates unsaturated fatty acids and could serve as the model to understand the regulation and trait formation in oil-accumulation crops. Here, we performed Ribosome footprint profiling combing with a multi-omics strategy towards vital time points during seed development, and finally constructed systematic profiling from transcription to proteomes. Additionally, we characterized the small open reading frames (ORFs) and revealed that the translational efficiencies of focused genes were highly influenced by their sequence features.
    RESULTS: The comprehensive multi-omics analysis of lipid metabolism was conducted in A. truncatum. We applied the Ribo-seq and RNA-seq techniques, and the analyses of transcriptional and translational profiles of seeds collected at 85 and 115 DAF were compared. Key members of biosynthesis-related structural genes (LACS, FAD2, FAD3, and KCS) were characterized fully. More meaningfully, the regulators (MYB, ABI, bZIP, and Dof) were identified and revealed to affect lipid biosynthesis via post-translational regulations. The translational features results showed that translation efficiency tended to be lower for the genes with a translated uORF than for the genes with a non-translated uORF. They provide new insights into the global mechanisms underlying the developmental regulation of lipid metabolism.
    CONCLUSIONS: We performed Ribosome footprint profiling combing with a multi-omics strategy in A. truncatum seed development, which provides an example of the use of Ribosome footprint profiling in deciphering the complex regulation network and will be useful for elucidating the metabolism of A. truncatum seed oil and the regulatory mechanisms.
    Keywords:  Acer truncatum; Ribosome profiling; Transcriptome
    DOI:  https://doi.org/10.1186/s12915-023-01564-8
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