Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins

ELife
Sondos SamandiXavier Roucou

Abstract

Recent functional, proteomic and ribosome profiling studies in eukaryotes have concurrently demonstrated the translation of alternative open-reading frames (altORFs) in addition to annotated protein coding sequences (CDSs). We show that a large number of small proteins could in fact be coded by these altORFs. The putative alternative proteins translated from altORFs have orthologs in many species and contain functional domains. Evolutionary analyses indicate that altORFs often show more extreme conservation patterns than their CDSs. Thousands of alternative proteins are detected in proteomic datasets by reanalysis using a database containing predicted alternative proteins. This is illustrated with specific examples, including altMiD51, a 70 amino acid mitochondrial fission-promoting protein encoded in MiD51/Mief1/SMCR7L, a gene encoding an annotated protein promoting mitochondrial fission. Our results suggest that many genes are multicoding genes and code for a large protein and one or several small proteins.

References

Oct 24, 1998·The Journal of Cell Biology·E SmirnovaA M van der Bliek
Nov 27, 1999·Science·D StockJ E Walker
May 29, 2000·Trends in Genetics : TIG·P RiceA Bleasby
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·S A WolfeC O Pabo
Feb 17, 2001·Current Opinion in Structural Biology·J H LaityP E Wright
Dec 18, 2001·Journal of Molecular Biology·M RemmE L Sonnhammer
Mar 1, 2003·Science·Joachim P SchmittChristine E Seidman
Feb 21, 2004·Bioinformatics·Robertson Craig, Ronald C Beavis
May 19, 2004·Proceedings of the National Academy of Sciences of the United States of America·Joel AbramowitzLutz Birnbaumer
Oct 12, 2004·Journal of Proteome Research·Lewis Y GeerStephen H Bryant
Mar 22, 2005·Gene·Michele IaconoGraziano Pesole
Jan 11, 2007·Journal of Microscopy·S Bolte, F P Cordelières
Apr 21, 2007·Methods in Cell Biology·Cristofol Vives-BauzaGiovanni Manfredi
May 12, 2007·Molecular Biology and Evolution·Daniel E Neafsey, James E Galagan
Mar 11, 2009·Current Protocols in Bioinformatics·Maja Tarailo-Graovac, Nansheng Chen
Sep 4, 2009·Genome Research·David G Knowles, Aoife McLysaght
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
May 19, 2010·Molecular and Cellular Biology·Calin-Bogdan ChiribauMaria Hatzoglou
Apr 12, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benoît VanderperreXavier Roucou
Apr 22, 2011·EMBO Reports·Catherine S PalmerMichael T Ryan
Nov 5, 2011·Genome Biology and Evolution·Yuh Chwen G Lee, Josephine A Reinhardt
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Jun 23, 2012·Nature·Anne-Ruxandra CarvunisMarc Vidal
Jul 24, 2012·Molecular Biology and Evolution·Niv SabathDavid Karlin
Aug 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Sooncheol LeeShu-Bing Qian
Nov 14, 2012·Proteomics·Jimmy K EngMichael R Hoopmann
Nov 20, 2012·Nature Chemical Biology·Sarah A SlavoffAlan Saghatelian
Nov 28, 2012·Science·Noam Stern-GinossarJonathan S Weissman
Jan 4, 2013·Molecular Biology of the Cell·Oliver C LosónDavid C Chan
Nov 5, 2013·Nucleic Acids Research·Audrey M MichelPavel V Baranov
Dec 3, 2013·The Journal of Biological Chemistry·Chien-fei LeeYijuang Chern
Jan 11, 2014·Science·Andrea PauliAlexander F Schier
Jan 24, 2014·Bioinformatics·Philip JonesSarah Hunter
Feb 12, 2014·Nature Reviews. Genetics·Shea J Andrews, Joseph A Rothnagel

❮ Previous
Next ❯

Citations

May 24, 2019·PLoS Genetics·Stephen Branden Van Oss, Anne-Ruxandra Carvunis
Jul 22, 2019·FEBS Letters·Sarah HaßdenteufelRichard Zimmermann
Jun 28, 2019·Bioinformatics·Elizabeth GuruceagaVictor Segura
Aug 8, 2019·Genome Research·Igor FesenkoVadim Govorun
Aug 12, 2020·Current Protocols in Bioinformatics·Marie A BrunetXavier Roucou
Aug 5, 2018·BMC Evolutionary Biology·Cemalettin BekpenDiethard Tautz
Apr 24, 2020·Nucleic Acids Research·Tristan CardonMichel Salzet
Mar 13, 2020·Nature Communications·Marie-Line DuboisFrançois-Michel Boisvert
Oct 10, 2018·Nucleic Acids Research·Marie A BrunetXavier Roucou
Nov 3, 2020·Computational and Structural Biotechnology Journal·Sebastien Leblanc, Marie A Brunet
Nov 29, 2020·Trends in Biochemical Sciences·Tristan CardonMichel Salzet
Nov 13, 2020·Nucleic Acids Research·Marie A BrunetXavier Roucou
Jan 10, 2021·Mechanisms of Ageing and Development·Jacek M WitkowskiTamas Fulop
Feb 18, 2021·The FEBS Journal·Dörte Schlesinger, Simon J Elsässer
Mar 2, 2021·Frontiers in Physiology·Alan A CohenXavier Roucou
Mar 11, 2021·Cell Reports·Maria Virginia Ruiz CuevasJonathan W Yewdell
May 26, 2020·Journal of Proteome Research·Xiongwen CaoSarah A Slavoff
Jun 10, 2021·Nucleic Acids Research·Hongwei WangZhi Xie
Jun 23, 2021·Database : the Journal of Biological Databases and Curation·Sebastien A ChoteauChristine Brun
Apr 24, 2021·Genome Biology and Evolution·Sophie BretonLiliana Milani
Aug 20, 2020·Journal of Proteome Research·Jürgen BartelDörte Becher
Dec 13, 2019·Analytical Chemistry·Tristan CardonIsabelle Fournier
Sep 15, 2018·Biochemistry·Annie RathoreAlan Saghatelian
Nov 12, 2020·Journal of the American Chemical Society·Lorenzo LafranchiSimon J Elsässer
Jul 10, 2021·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Diego Guerra-AlmeidaRodrigo Nunes-da-Fonseca
Oct 2, 2021·Proceedings of the National Academy of Sciences of the United States of America·Divya Ram JayaramEtta Livneh
Oct 7, 2021·Nature Reviews. Genetics·Bradley W WrightPaul R Jaschke
Oct 20, 2021·ACS Applied Materials & Interfaces·Jiaju ShiShu-Sheng Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
footprinting
affinity purification
Confocal microscopy
co-immunoprecipitation
transfection
protein assay
Assay

Software Mentioned

viz genome browser
Interpro
bowtie2
BLAST
proteoQC R
BlastP
IMS
RepeatMasker
SignalP
InterProscan

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.