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https://www.readbyqxmd.com/read/29897761/enrichment-based-proteogenomics-identifies-microproteins-missing-proteins-and-novel-smorfs-in-saccharomyces-cerevisiae
#1
Cuitong He, Chenxi Jia, Yao Zhang, Ping Xu
Microproteins are peptides composed of 100 amino acids (AA) or fewer, encoded by small open reading frames (smORFs). It has been demonstrated that microproteins participate in and regulate a wide range of functions in cells. However, the annotation and identification of microproteins is challenging in part owing to their low molecular weight, low abundancy, and hydrophobicity. These factors have led to the unannotation of smORFs in genome processing and have made their identification at the protein level difficult...
July 6, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29786095/high-throughput-creation-and-functional-profiling-of-dna-sequence-variant-libraries-using-crispr-cas9-in-yeast
#2
Xiaoge Guo, Alejandro Chavez, Angela Tung, Yingleong Chan, Christian Kaas, Yi Yin, Ryan Cecchi, Santiago Lopez Garnier, Eric D Kelsic, Max Schubert, James E DiCarlo, James J Collins, George M Church
Construction and characterization of large genetic variant libraries is essential for understanding genome function, but remains challenging. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions, and insertions) with an efficiency of 80-100% in yeast, along with methods for tracking their fitness en masse. We demonstrate the utility of our approach by characterizing the DNA helicase SGS1 with small tiling deletion mutants that span the length of the protein and a series of point mutations against highly conserved residues in the protein...
July 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29721095/encoding-activities-of-non-coding-rnas
#3
REVIEW
Yanan Pang, Chuanbin Mao, Shanrong Liu
The universal expression of various non-coding RNAs (ncRNAs) is now considered the main feature of organisms' genomes. Many regions in the genome are transcribed but not annotated to encode proteins, yet contain small open reading frames (smORFs). A widely accepted opinion is that a vast majority of ncRNAs are not further translated. However, increasing evidence underlines a series of intriguing translational events from the ncRNAs, which were previously considered to lack coding potential. Recent studies also suggest that products derived from such novel translational events display important regulatory functions in many fundamental biological and pathological processes...
2018: Theranostics
https://www.readbyqxmd.com/read/29675032/fspp-a-tool-for-genome-wide-prediction-of-smorf-encoded-peptides-and-their-functions
#4
Hui Li, Li Xiao, Lili Zhang, Jiarui Wu, Bin Wei, Ninghui Sun, Yi Zhao
smORFs are small open reading frames of less than 100 codons. Recent low throughput experiments showed a lot of smORF-encoded peptides (SEPs) played crucial rule in processes such as regulation of transcription or translation, transportation through membranes and the antimicrobial activity. In order to gather more functional SEPs, it is necessary to have access to genome-wide prediction tools to give profound directions for low throughput experiments. In this study, we put forward a functional smORF-encoded peptides predictor (FSPP) which tended to predict authentic SEPs and their functions in a high throughput method...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29584760/the-influence-of-transcript-assembly-on-the-proteogenomics-discovery-of-microproteins
#5
Jiao Ma, Alan Saghatelian, Maxim Nikolaievich Shokhirev
Proteogenomics methods have identified many non-annotated protein-coding genes in the human genome. Many of the newly discovered protein-coding genes encode peptides and small proteins, referred to collectively as microproteins. Microproteins are produced through ribosome translation of small open reading frames (smORFs). The discovery of many smORFs reveals a blind spot in traditional gene-finding algorithms for these genes. Biological studies have found roles for microproteins in cell biology and physiology, and the potential that there exists additional bioactive microproteins drives the interest in detection and discovery of these molecules...
2018: PloS One
https://www.readbyqxmd.com/read/29306967/identification-of-tarsal-less-peptides-from-the-silkworm-bombyx-mori
#6
Guangli Cao, Yongchang Gong, Xiaolong Hu, Min Zhu, Zi Liang, Lixu Huang, Lei Yu, Jian Xu, Kun Li, Mian Sahib Zar, Renyu Xue, Chengliang Gong
The polycistronic and non-canonical gene tarsal-less (tal, known as pri) was reported to be required for embryonic and imaginal development in Drosophila; however, there are few reports of the tal gene in the silkworm Bombyx mori. Here, we cloned a tal-like (Bmtal) gene, and a sequence analysis showed that the Bmtal cDNA (1661 bp) contains five small open reading frames (smORFs) (A1, A2, A3, A4, and B) that encode short peptides of 11-12 (A1-A4) amino acid residues containing an LDPTG(E)L(Q)(V)Y motif that is conserved in Drosophila Tal, as well as a 32-amino-acid B peptide...
February 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29138516/the-functions-and-unique-features-of-long-intergenic-non-coding-rna
#7
REVIEW
Julia D Ransohoff, Yuning Wei, Paul A Khavari
Long intergenic non-coding RNA (lincRNA) genes have diverse features that distinguish them from mRNA-encoding genes and exercise functions such as remodelling chromatin and genome architecture, RNA stabilization and transcription regulation, including enhancer-associated activity. Some genes currently annotated as encoding lincRNAs include small open reading frames (smORFs) and encode functional peptides and thus may be more properly classified as coding RNAs. lincRNAs may broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity through a diversity of mechanisms, highlighting our rapidly evolving understanding of the non-coding genome...
March 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29039980/advances-in-the-chromosome-centric-human-proteome-project-looking-to-the-future
#8
REVIEW
Young-Ki Paik, Gilbert S Omenn, William S Hancock, Lydie Lane, Christopher M Overall
The mission of the Chromosome-Centric Human Proteome Project (C-HPP), is to map and annotate the entire predicted human protein set (~20,000 proteins) encoded by each chromosome. The initial steps of the project are focused on 'missing proteins (MPs)', which lacked documented evidence for existence at protein level. In addition to remaining 2,579 MPs, we also target those annotated proteins having unknown functions, uPE1 proteins, alternative splice isoforms and post-translational modifications. We also consider how to investigate various protein functions involved in cis-regulatory phenomena, amplicons lncRNAs and smORFs...
December 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/29039649/comparative-membrane-proteomics-reveals-a-nonannotated-e-coli-heat-shock-protein
#9
COMPARATIVE STUDY
Peijia Yuan, Nadia G D'Lima, Sarah A Slavoff
Recent advances in proteomics and genomics have enabled discovery of thousands of previously nonannotated small open reading frames (smORFs) in genomes across evolutionary space. Furthermore, quantitative mass spectrometry has recently been applied to analysis of regulated smORF expression. However, bottom-up proteomics has remained relatively insensitive to membrane proteins, suggesting they may have been underdetected in previous studies. In this report, we add biochemical membrane protein enrichment to our previously developed label-free quantitative proteomics protocol, revealing a never-before-identified heat shock protein in Escherichia coli K12...
January 9, 2018: Biochemistry
https://www.readbyqxmd.com/read/28861998/comparative-proteomics-enables-identification-of-nonannotated-cold-shock-proteins-in-e-coli
#10
Nadia G D'Lima, Alexandra Khitun, Aaron D Rosenbloom, Peijia Yuan, Brandon M Gassaway, Karl W Barber, Jesse Rinehart, Sarah A Slavoff
Recent advances in mass spectrometry-based proteomics have revealed translation of previously nonannotated microproteins from thousands of small open reading frames (smORFs) in prokaryotic and eukaryotic genomes. Facile methods to determine cellular functions of these newly discovered microproteins are now needed. Here, we couple semiquantitative comparative proteomics with whole-genome database searching to identify two nonannotated, homologous cold shock-regulated microproteins in Escherichia coli K12 substr...
October 6, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28825667/viral-infection-identifies-micropeptides-differentially-regulated-in-smorf-containing-lncrnas
#11
Brandon S Razooky, Benedikt Obermayer, Joshua Biggs O'May, Alexander Tarakhovsky
Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, studies utilizing next-generation sequencing technologies show that a subset of the >10,000 lncRNAs in the mammalian genome contain small open reading frames (smORFs) associated with active translation, i...
August 21, 2017: Genes
https://www.readbyqxmd.com/read/28759257/in-search-of-lost-small-peptides
#12
REVIEW
Serge Plaza, Gerben Menschaert, François Payre
A large body of evidence indicates that genome annotation pipelines have biased our view of coding sequences because they generally undersample small proteins and peptides. The recent development of genome-wide translation profiling reveals the prevalence of small/short open reading frames (smORFs or sORFs), which are scattered over all classes of transcripts, including both mRNAs and presumptive long noncoding RNAs. Proteomic approaches further confirm an unexpected variety of smORF-encoded peptides (SEPs), representing an overlooked reservoir of bioactive molecules...
October 6, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28747815/identification-of-very-small-open-reading-frames-in-the-genomes-of-holmes-jungle-virus-ord-river-virus-and-wongabel-virus-of-the-genus-hapavirus-family-rhabdoviridae
#13
REVIEW
Aneta Gubala, Susan Walsh, Jane McAllister, Richard Weir, Steven Davis, Lorna Melville, Ian Mitchell, Dieter Bulach, Penny Gauci, Alex Skvortsov, David Boyle
Viruses of the family Rhabdoviridae infect a broad range of hosts from a variety of ecological and geographical niches, including vertebrates, arthropods, and plants. The arthropod-transmitted members of this family display considerable genetic diversity and remarkable genomic flexibility that enable coding for various accessory proteins in different locations of the genome. Here, we describe the genome of Holmes Jungle virus, isolated from Culex annulirostris mosquitoes collected in northern Australia, and make detailed comparisons with the closely related Ord River and Wongabel viruses, with a focus on identifying very small open reading frames (smORFs) in their genomes...
2017: Evolutionary Bioinformatics Online
https://www.readbyqxmd.com/read/28698598/classification-and-function-of-small-open-reading-frames
#14
Juan-Pablo Couso, Pedro Patraquim
Small open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans...
September 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28589727/identification-of-microprotein-protein-interactions-via-apex-tagging
#15
COMPARATIVE STUDY
Qian Chu, Annie Rathore, Jolene K Diedrich, Cynthia J Donaldson, John R Yates, Alan Saghatelian
Microproteins are peptides and small proteins encoded by small open reading frames (smORFs). Newer technologies have led to the recent discovery of hundreds to thousands of new microproteins. The biological functions of a few microproteins have been elucidated, and these microproteins have fundamental roles in biology ranging from limb development to muscle function, highlighting the value of characterizing these molecules. The identification of microprotein-protein interactions (MPIs) has proven to be a successful approach to the functional characterization of these genes; however, traditional immunoprecipitation methods result in the enrichment of nonspecific interactions for microproteins...
July 5, 2017: Biochemistry
https://www.readbyqxmd.com/read/28569745/the-microprotein-minion-controls-cell-fusion-and-muscle-formation
#16
Qiao Zhang, Ajay A Vashisht, Jason O'Rourke, Stéphane Y Corbel, Rita Moran, Angelica Romero, Loren Miraglia, Jia Zhang, Eric Durrant, Christian Schmedt, Srinath C Sampath, Srihari C Sampath
Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, their function remains to be determined. Skeletal muscle development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process. Here we report the identification of Minion (microprotein inducer of fusion), a smORF encoding an essential skeletal muscle specific microprotein. Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally and demonstrate a marked reduction in fused muscle fibres...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/27918561/a-human-microprotein-that-interacts-with-the-mrna-decapping-complex
#17
Nadia G D'Lima, Jiao Ma, Lauren Winkler, Qian Chu, Ken H Loh, Elizabeth O Corpuz, Bogdan A Budnik, Jens Lykke-Andersen, Alan Saghatelian, Sarah A Slavoff
Proteomic detection of non-annotated microproteins indicates the translation of hundreds of small open reading frames (smORFs) in human cells, but whether these microproteins are functional or not is unknown. Here, we report the discovery and characterization of a 7-kDa human microprotein we named non-annotated P-body dissociating polypeptide (NoBody). NoBody interacts with mRNA decapping proteins, which remove the 5' cap from mRNAs to promote 5'-to-3' decay. Decapping proteins participate in mRNA turnover and nonsense-mediated decay (NMD)...
February 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/27853904/overexpression-of-smorf-ynr034w-a-ego4-in-saccharomyces-cerevisiae-increases-the-fermentative-efficiency-of-agave-tequilana-weber-must
#18
Naurú Idalia Vargas-Maya, Gloria Angélica González-Hernández, Israel Enrique Padilla-Guerrero, Juan Carlos Torres-Guzmán
Fermentative processes are widely used to produce food, beverages and biofuels. Saccharomyces cerevisiae is an efficient ethanol-producing microorganism. However, a concentration of high ethanol and other metabolites can affect yeast viability and decrease the ethanol yield. Many studies have focused on improving the fermentative efficiency, mostly through the genetic engineering of genes that have a direct impact on specific metabolic pathways. In the present study, we characterized a small open reading frame encoding a protein with an unknown function and biological role termed YNR034W-A...
January 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27261332/new-peptides-under-the-s-orf-ace-of-the-genome
#19
REVIEW
Jose I Pueyo, Emile G Magny, Juan P Couso
Hundreds, perhaps thousands of previously unidentified functional small peptides could exist in most genomes, but these sequences have been generally overlooked. The discovery of genes encoding small peptides with important functions in different organisms has ignited the interest in these sequences and led to an increasing amount of effort towards their identification. Here, we review the advances, both computational and biochemical, that are leading the way in the discovery of putatively functional small open reading frame genes (smORFs), as well as the functional studies that have been carried out as a consequence of these searches...
August 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27015288/hemotin-a-regulator-of-phagocytosis-encoded-by-a-small-orf-and-conserved-across-metazoans
#20
José I Pueyo, Emile G Magny, Christopher J Sampson, Unum Amin, Iwan R Evans, Sarah A Bishop, Juan P Couso
Translation of hundreds of small ORFs (smORFs) of less than 100 amino acids has recently been revealed in vertebrates and Drosophila. Some of these peptides have essential and conserved cellular functions. In Drosophila, we have predicted a particular smORF class encoding ~80 aa hydrophobic peptides, which may function in membranes and cell organelles. Here, we characterise hemotin, a gene encoding an 88aa transmembrane smORF peptide localised to early endosomes in Drosophila macrophages. hemotin regulates endosomal maturation during phagocytosis by repressing the cooperation of 14-3-3ζ with specific phosphatidylinositol (PI) enzymes...
March 2016: PLoS Biology
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