Found in translation: functions and evolution of a recently discovered alternative proteome

Landry, Christian R.; Zhong, Xiao; Nielly‐Thibault, Lou; Roucou, Xavier

doi:10.1016/j.sbi.2015.02.017

Cited by 52 publications

(55 citation statements)

References 48 publications

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“…Indeed, the functional characterization of selected examples of μ-proteins has revealed their critical involvement in processes such as quorum sensing or interspecies communication [2], regulatory functions [3–6] and in the formation of multi-subunit protein complexes. An increasing number of μ-proteins is being discovered also in eukaryotes [7–10], and archaea [11], indicating their ubiquity in all three domains of life. Nevertheless, the likely diverse functions of short proteins are largely unknown, even for simple unicellular bacteria.…”

Section: Introductionmentioning

confidence: 99%

Small proteins in cyanobacteria provide a paradigm for the functional analysis of the bacterial micro-proteome

et al. 2016

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BackgroundDespite their versatile functions in multimeric protein complexes, in the modification of enzymatic activities, intercellular communication or regulatory processes, proteins shorter than 80 amino acids (μ-proteins) are a systematically underestimated class of gene products in bacteria. Photosynthetic cyanobacteria provide a paradigm for small protein functions due to extensive work on the photosynthetic apparatus that led to the functional characterization of 19 small proteins of less than 50 amino acids. In analogy, previously unstudied small ORFs with similar degrees of conservation might encode small proteins of high relevance also in other functional contexts.ResultsHere we used comparative transcriptomic information available for two model cyanobacteria, Synechocystis sp. PCC 6803 and Synechocystis sp. PCC 6714 for the prediction of small ORFs. We found 293 transcriptional units containing candidate small ORFs ≤80 codons in Synechocystis sp. PCC 6803, also including the known mRNAs encoding small proteins of the photosynthetic apparatus. From these transcriptional units, 146 are shared between the two strains, 42 are shared with the higher plant Arabidopsis thaliana and 25 with E. coli. To verify the existence of the respective μ-proteins in vivo, we selected five genes as examples to which a FLAG tag sequence was added and re-introduced them into Synechocystis sp. PCC 6803. These were the previously annotated gene ssr1169, two newly defined genes norf1 and norf4, as well as nsiR6 (nitrogen stress-induced RNA 6) and hliR1(high light-inducible RNA 1) , which originally were considered non-coding. Upon activation of expression via the Cu2+.responsive petE promoter or from the native promoters, all five proteins were detected in Western blot experiments.ConclusionsThe distribution and conservation of these five genes as well as their regulation of expression and the physico-chemical properties of the encoded proteins underline the likely great bandwidth of small protein functions in bacteria and makes them attractive candidates for functional studies.

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Section: Introductionmentioning

confidence: 99%

Small proteins in cyanobacteria provide a paradigm for the functional analysis of the bacterial micro-proteome

et al. 2016

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“…After being transcribed by RNA polymerase II, all of these lncRNAs are 5′-capped, 3′-polyadenylated, spliced and some of them will be exported to cytoplasm [7]. It is recently reported that lncRNAs may contain short open reading frame (sORF, less than 100 codons) and hence produce small peptides, although these peptides used to be neglected by classic open reading frame prediction based on a cutoff of 100 codons as minimum length [8–10]. …”

Section: Introductionmentioning

confidence: 99%

Dysregulation of long non-coding RNA in breast cancer: an overview of mechanism and clinical implication

Xiong

et al. 2016

Oncotarget

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Long non-coding RNAs (lncRNAs), which occupy nearly 98% of genome, have crucial roles in cancer development, including breast cancer. Breast cancer is a disease with high incidence. Despite of recent progress in understanding the molecular mechanisms and combined therapy strategies, the functions and mechanisms of lncRNAs in breast cancer remains unclear. This review presents the currently basic knowledge and research approaches of lncRNAs. We also highlight the latest advances of seven classic lncRNAs and three novel lncRNAs in breast cancer, elucidating their mechanisms and possible therapeutic targets. Additionally, association between lncRNA and specific molecular subtype of breast cancer is reported. Lastly, we briefly delineate the potential roles of lncRNAs in clinical applications as biomarkers and treatment targets.

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“…Previous studies have shown that identification of low-molecular weight proteins pose many challenges due to the low number of observable peptides for MS/MS detection. 11,15 Taking into account the added challenges of recovering hydrophobic peptides, our approach demonstrated the capability to identify and validate even small hydrophobic membrane proteins.…”

Section: Resultsmentioning

confidence: 99%

Mining Missing Membrane Proteins by High-pH Reverse-Phase StageTip Fractionation and Multiple Reaction Monitoring Mass Spectrometry

et al. 2015

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Despite significant efforts in the past decade towards complete mapping of the human proteome, 3564 proteins (neXtProt, 09-2014) are still “missing proteins”. Over one-third of these missing proteins are annotated as membrane proteins, owing to their relatively challenging accessibility with standard shotgun proteomics. Using non-small cell lung cancer (NSCLC) as a model study, we aim to mine missing proteins from disease-associated membrane proteome, which may be still largely under-represented. To increase identification coverage, we employed Hp-RP StageTip pre-fractionation of membrane-enriched samples from 11 NSCLC cell lines. Analysis of membrane samples from 20 pairs of tumor and adjacent normal lung tissue were incorporated to include physiologically expressed membrane proteins. Using multiple search engines (X!Tandem, Comet and Mascot) and stringent evaluation of FDR (MAYU and PeptideShaker), we identified 7702 proteins (66% membrane proteins) and 178 missing proteins (74 membrane proteins) with PSM-, peptide-, and protein-level FDR of 1%. Through multiple reaction monitoring (MRM) using synthetic peptides, we provided additional evidences for 8 missing proteins including 7 with transmembrane helix domains (TMH). This study demonstrates that mining missing proteins focused on cancer membrane sub-proteome can greatly contribute to map the whole human proteome. All data were deposited into ProteomeXchange with the identifier PXD002224.

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Found in translation: functions and evolution of a recently discovered alternative proteome

Cited by 52 publications

References 48 publications

Small proteins in cyanobacteria provide a paradigm for the functional analysis of the bacterial micro-proteome

Small proteins in cyanobacteria provide a paradigm for the functional analysis of the bacterial micro-proteome

Dysregulation of long non-coding RNA in breast cancer: an overview of mechanism and clinical implication

Mining Missing Membrane Proteins by High-pH Reverse-Phase StageTip Fractionation and Multiple Reaction Monitoring Mass Spectrometry

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