Quantitative Profiling of Peptides from RNAs classified as non-coding

Only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into proteins, and it is generally assumed that a large portion of transcribed sequences—including introns and several classes of noncoding RNAs (ncRNAs)—do not give rise to peptide products. A systematic examination of translation and physiological regulation of ncRNAs has not been conducted. Here we use computational methods to identify the products of non-canonical translation in mouse neurons by analysing unannotated transcripts in combination with proteomic data. This study supports the existence of non-canonical translation products from both intragenic and extragenic genomic regions, including peptides derived from antisense transcripts and introns. Moreover, the studied novel translation products exhibit temporal regulation similar to that of proteins known to be involved in neuronal activity processes. These observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential. A large portion of the transcribed genome—such as introns and noncoding RNAs—is believed to not be translated into protein products. Here, the authors provide evidence for the existence of regulated peptide products that are translated from transcribed sequences generally characterized as noncoding.

• Publication year

  2014

• Venue

  Nature Communications

• Publication date

  2014-11-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/ncomms6429PMID 25403355PMCID 4416701
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation

  2014cited by this paper
• Co‐regulation proteomics reveals substrates and mechanisms of APC/C‐dependent degradation

  2014cited by this paper
• Toddler: An Embryonic Signal That Promotes Cell Movement via Apelin Receptors

  2014cited by this paper
• A Non-parametric Cutout Index for Robust Evaluation of Identified Proteins*

  2013cited by this paper
• Conserved Regulation of Cardiac Calcium Uptake by Peptides Encoded in Small Open Reading Frames

  2013cited by this paper
• Deep Proteome Coverage Based on Ribosome Profiling Aids Mass Spectrometry-based Protein and Peptide Discovery and Provides Evidence of Alternative Translation Products and Near-cognate Translation Initiation Events*

  2013cited by this paper
• Divergent transcription: a driving force for new gene origination?

  2013cited by this paper
• Proto-genes and de novo gene birth

  2012cited by this paper
• Landscape of transcription in human cells

  2012cited by this paper
• A map of the cis-regulatory sequences in the mouse genome

  2012cited by this paper
• Integrated genome analysis suggests that most conserved non-coding sequences are regulatory factor binding sites

  2012cited by this paper
• Peptidomic discovery of short open reading frame-encoded peptides in human cells

  2012cited by this paper
• Shotgun proteomics aids discovery of novel protein-coding genes, alternative splicing, and "resurrected" pseudogenes in the mouse genome.

  2011cited by this paper
• Naming 'junk': Human non-protein coding RNA (ncRNA) gene nomenclature

  2011cited by this paper
• Optimization of cell lysis and protein digestion protocols for the analysis of HeLa S3 cells by LC‐MS/MS

  2011cited by this paper
• Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes.

  2011cited by this paper
• Computational protein profile similarity screening for quantitative mass spectrometry experiments

  2010cited by this paper
• Biochemical principles of small RNA pathways.

  2010cited by this paper
• Evolution and functions of long noncoding RNAs.

  2009cited by this paper
• The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs

  2009cited by this paper
• What do natural antisense transcripts regulate?

  2009cited by this paper
• Differentiating Protein-Coding and Noncoding RNA: Challenges and Ambiguities

  2008cited by this paper
• Divergent Transcription from Active Promoters

  2008cited by this paper
• Robust and Sensitive iTRAQ Quantification on an LTQ Orbitrap Mass Spectrometer*S

  2008cited by this paper
• Robust prediction of the MASCOT score for an improved quality assessment in mass spectrometric proteomics.

  2008cited by this paper
• Diversity of Translation Start Sites May Define Increased Complexity of the Human Short ORFeome*S

  2007cited by this paper
• Genome annotation past, present, and future: how to define an ORF at each locus.

  2005cited by this paper
• Aligning multiple genomic sequences with the threaded blockset aligner.

  2004cited by this paper
• Acknowledgements

  2003cited by this paper
• Large-Scale Transcriptional Activity in Chromosomes 21 and 22

  2002cited by this paper

• Coordinated expression of retained introns and poison exons in renal cell carcinoma

  2025cites this paper
• Harnessing Noncanonical Proteins for Next‐Generation Drug Discovery and Diagnosis

  2025influential citation
• ncRNA Coding Potential Prediction Using BiLSTM and Transformer Encoder-Based Model

  2024cites this paper
• The ribosome profiling landscape of yeast reveals a high diversity in pervasive translation

  2024cites this paper
• Aberrant spliceosome activity via elevated intron retention and upregulation and phosphorylation of SF3B1 in chronic lymphocytic leukemia

  2024cites this paper
• Cis to trans: small ORF functions emerging through evolution.

  2024cites this paper
• A novel human protein-coding locus identified using a targeted RNA enrichment technique

  2024cites this paper
• Evidence for widespread existence of functional novel and non-canonical human transcripts

  2023cites this paper
• The Ribosome Profiling landscape of yeast reveals a high diversity in pervasive translation

  2023cites this paper
• Integrative systems biology characterizes immune-mediated neurodevelopmental changes in murine Zika virus microcephaly

  2023cites this paper
• LncRNA-encoded peptides: unveiling their significance in cardiovascular physiology and pathology - current research insights.

  2023cites this paper
• Advances in peptides encoded by non-coding RNAs: A cargo in exosome

  2022cites this paper
• Therapeutic Potential of Long Non-Coding RNAs of HIV-1, SARS-CoV-2, and Endogenous Retroviruses

  2022cites this paper
• Exploring the Peptide Potential of Genomes.

  2022cites this paper
• The construct of schizophrenia as a human-specific condition.

  2022cites this paper
• Proteomics‐driven identification of short open reading frame‐encoded peptides

  2022cites this paper
• A platform for curated products from novel open reading frames prompts reinterpretation of disease variants

  2021cites this paper
• Understanding small diversity through a comprehensive transcription

  2021cites this paper
• Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions

  2021cites this paper
• Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological functions

  2021cites this paper
• In silico identification of novel open reading frames in Plasmodium falciparum oocyte and salivary gland sporozoites using proteogenomics framework

  2021cites this paper
• Identification of a micropeptide and multiple secondary cell genes that modulate Drosophila male reproductive success

  2021cites this paper
• Intergenic ORFs as elementary structural modules of de novo gene birth and protein evolution

  2021cites this paper
• Understanding small ORF diversity through a comprehensive transcription feature classification

  2021cites this paper
• In-Depth Annotation of the Drosophila Bithorax-Complex Reveals the Presence of Several Alternative ORFs That Could Encode for Motif-Rich Peptides

  2021cites this paper
• The Small Open Reading Frame‐Encoded Peptides: Advances in Methodologies and Functional Studies

  2021cites this paper
• Novel open reading frames in human accelerated regions and transposable elements reveal new leads to understand schizophrenia and bipolar disorder

  2021cites this paper
• Rapid speciation of cichlids fishes may be explained by evolutionary divergence of novel open reading frames

  2020cites this paper
• A Critical Review of Proteomic Studies in Gestational Diabetes Mellitus

  2020cites this paper
• Translation of noncoding RNAs and cancer.

  2020cites this paper
• Evolutionary divergence of novel open reading frames in cichlids speciation

  2020cites this paper
• Use of short-read RNA-Seq data to identify transcripts that can translate novel ORFs

  2020cites this paper
• Proteins encoded by Novel ORFs have increased disorder but can be biochemically regulated and harbour deleterious mutations

  2019cites this paper
• Proteins encoded by Novel ORFs have increased disorder but can be biochemically regulated and harbour pathogenic mutations

  2019cites this paper
• Cell-Type-Specific Profiling of Alternative Translation Identifies Regulated Protein Isoform Variation in the Mouse Brain

  2019influential citation
• Translational products encoded by novel ORFs may form protein-like structures and have biological functions

  2019cites this paper
• Small Proteins Encoded by Unannotated ORFs are Rising Stars of the Proteome, Confirming Shortcomings in Genome Annotations and Current Vision of an mRNA

  2018cites this paper
• Cell type specific profiling of alternative translation identifies novel protein isoforms in the mouse brain

  2018cites this paper
• Strategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls.

  2018cites this paper
• Impact of Noncoding Part of the Genome on the Proteome Plasticity of the Eukaryotic Cell

  2018cites this paper
• Roles of Long Noncoding RNAs and Circular RNAs in Translation.

  2018cites this paper
• Mining for Small Translated ORFs.

  2018cites this paper
• Encoding activities of non-coding RNAs

  2018cites this paper
• Annual Review of Cell and Developmental Biology In Search of Lost Small Peptides

  2017cites this paper
• Identification and Prioritisation of Variants in the Short Open-Reading Frame Regions of the Human Genome

  2017cites this paper
• Distinct types of short open reading frames are translated in plant cells

  2017cites this paper
• Onco-proteogenomics: Multi-omics level data integration for accurate phenotype prediction

  2017cites this paper
• Challenges in defining the role of intron retention in normal biology and disease.

  2017cites this paper
• In Search of Lost Small Peptides.

  2017cites this paper
• Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins

  2017cites this paper
• Deep transcriptome annotation suggests that small and large proteins encoded in the same genes often cooperate

  2017cites this paper
• A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology

  2017cites this paper
• Onco-proteogenomic exploration of variant peptide detection in disease models and clinical specimens

  2017cites this paper
• Small Peptides as Newcomers in the Control of Drosophila Development.

  2016cites this paper
• Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation.

  2016cites this paper
• Commentary: Primary Transcripts of microRNAs Encode Regulatory Peptides

  2016cites this paper
• Global and cell-type specific properties of lincRNAs with ribosome occupancy

  2016cites this paper
• JUMPg: An Integrative Proteogenomics Pipeline Identifying Unannotated Proteins in Human Brain and Cancer Cells.

  2016cites this paper
• The need to revisit published data: A concept and framework for complementary proteomics

  2016cites this paper
• Characterization of the recovery of mechanical properties of ion-implanted diamond after thermal annealing

  2016cites this paper
• Softening the ultra-stiff: Controlled variation of Young’s modulus in single-crystal diamond by ion implantation

  2016cites this paper
• The Landscape of long non-coding RNA classification

  2015cites this paper
• Comprehensive identification and characterization of conserved small ORFs in animals

  2015cites this paper
• The Landscape of long noncoding RNA classification.

  2015cites this paper
• Found in translation: functions and evolution of a recently discovered alternative proteome.

  2015cites this paper
• The Plant Peptidome: An Expanding Repertoire of Structural Features and Biological Functions[OPEN]

  2015cites this paper
• Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination

  2015cites this paper
• Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs

  2015cites this paper
• Extensive identification and analysis of conserved small ORFs in animals

  2015cites this paper