bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2020–11–01
three papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells.
  2. LncRBase V.2: an updated resource for multispecies lncRNAs and ClinicLSNP hosting genetic variants in lncRNAs for cancer patients.
  3. sORF-encoded polypeptide SEP1 is a novel virulence factor of Phytophthora pathogens.
  1. Elife. 2020 Oct 28. pii: e53734. [Epub ahead of print]9
    A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells.
    Xiao Ling Li, Lőrinc Pongor, Wei Tang, Sudipto Das, Bruna R Muys, Matthew F Jones, Sarah B Lazar, Emily A Dangelmaier, Corrine Cr Hartford, Ioannis Grammatikakis, Qinyu Hao, Qinyu Sun, Aaron Schetter, Jennifer L Martindale, BinWu Tang, Lisa M Jenkins, Ana I Robles, Robert L Walker, Stefan Ambs, Raj Chari, Svetlana A Shabalina, Myriam Gorospe, Perwez S Hussain, Curtis C Harris, Paul S Meltzer, Kannanganattu V Prasanth, Mirit I Aladjem, Thorkell Andresson, Ashish Lal.
      Long noncoding RNAs (lncRNAs) are often associated with polysomes, indicating coding potential. However, only a handful of endogenous proteins encoded by putative lncRNAs have been identified and assigned a function. Here, we report the discovery of a putative gastrointestinal tract-specific lncRNA (LINC00675) that is regulated by the pioneer transcription factor FOXA1 and encodes a conserved small protein of 79 amino acids which we termed FORCP (FOXA1-Regulated Conserved Small Protein). FORCP transcript is undetectable in most cell types but is abundant in well-differentiated colorectal cancer (CRC) cells where it functions to inhibit proliferation, clonogenicity and tumorigenesis. The epitope-tagged and endogenous FORCP protein predominantly localizes to the endoplasmic reticulum (ER). In response to ER stress, FORCP depletion results in decreased apoptosis. Our findings on the initial characterization of FORCP demonstrate that FORCP is a novel, conserved small protein encoded by a mis-annotated lncRNA that regulates apoptosis and tumorigenicity in well-differentiated CRC cells.
    Keywords:  cancer biology; chromosomes; gene expression; human
    DOI:  https://doi.org/10.7554/eLife.53734
  2. RNA Biol. 2020 Oct 28. 1-16
    LncRBase V.2: an updated resource for multispecies lncRNAs and ClinicLSNP hosting genetic variants in lncRNAs for cancer patients.
    Troyee Das, Aritra Deb, Sibun Parida, Sudip Mondal, Sunirmal Khatua, Zhumur Ghosh.
      The recent discovery of long non-coding RNA as a regulatory molecule in the cellular system has altered the concept of the functional aptitude of the genome. Since our publication of the first version of LncRBase in 2014, there has been an enormous increase in the number of annotated lncRNAs of multiple species other than Human and Mouse. LncRBase V.2 hosts information of 549,648 lncRNAs corresponding to six additional species besides Human and Mouse, viz. Rat, Fruitfly, Zebrafish, Chicken, Cow and C.elegans. It provides additional distinct features such as (i) Transcription Factor Binding Site (TFBS) in the lncRNA promoter region, (ii) sub-cellular localization pattern of lncRNAs (iii) lnc-pri-miRNAs (iv) Possible small open reading frames (sORFs) within lncRNA. (v) Manually curated information of interacting target molecules and disease association of lncRNA genes (vi) Distribution of lncRNAs across multiple tissues of all species. Moreover, we have hosted ClinicLSNP within LncRBase V.2. ClinicLSNP has a comprehensive catalogue of lncRNA variants present within breast, ovarian, and cervical cancer inferred from 561 RNA-Seq data corresponding to these cancers. Further, we have checked whether these lncRNA variants overlap with (i)Repeat elements,(ii)CGI, (iii)TFBS within lncRNA loci (iv)SNP localization in trait-associated Linkage Disequilibrium(LD) region, (v)predicted the potentially pathogenic variants and (vi)effect of SNP on lncRNA secondary structure. Overall, LncRBaseV.2 is a user-friendly database to survey, search and retrieve information about multi-species lncRNAs. Further, ClinicLSNP will serve as a useful resource for cancer specific lncRNA variants and their related information. The database is freely accessible and available at http://dibresources.jcbose.ac.in/zhumur/lncrbase2/.
    Keywords:  Long non-coding RNA; clinicLSNP; female cancer; lncRNA variant; lncrbase; sORFs; sub-cellular localization
    DOI:  https://doi.org/10.1080/15476286.2020.1833529
  3. Mol Plant Microbe Interact. 2020 Oct 26.
    sORF-encoded polypeptide SEP1 is a novel virulence factor of Phytophthora pathogens.
    Nan Wang, Zhiyuan Yin, Weiwei Duan, Xiong Zhang, Lei Pi, Yifang Zhang, Daolong Dou.
      Diseases caused by the notorious Phytophthora species result in enormous economic losses to crops and forests. Increasing evidence suggests that small open reading frame-encoded polypeptides (SEPs) participate in environmental responses of animals, plants, and fungi. However, it remains largely unknown whether Phytophthora pathogens produce SEPs. Here, we systematically predicted and identified 96 SEP candidates in P. capsici. Among them, three may induce stable cell death in Nicotiana benthamiana. Phytophthora-specific and conserved SEP1 facilitated P. capsici infection. PcSEP1-induced cell death is BAK1- and SOBIR1-independent and is correlated to its virulence function. Finally, PcSEP1 may be targeted to the apoplast for carrying out its functions, for which the C-terminus is indispensable. Together, our results demonstrated that SEP1 is a new virulence factor, and previously unknown SEPs may act as effector proteins in Phytophthora pathogens.
    DOI:  https://doi.org/10.1094/MPMI-06-20-0160-R
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