scholarly journals Generation of ENSEMBL-based proteogenomics databases boosts the identification of non-canonical peptides.

2021 ◽  
Author(s):  
Husen M Umer ◽  
Yafeng Zhu ◽  
Julianus Pfeuffer ◽  
Timo Sachsenberg ◽  
Janne Lehtio ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Protein Sequences ◽  
Cell Type ◽  
Multiple Sources ◽  
Protein Coding ◽  
Genomic Variants ◽  
Cell Type Specific ◽  
Public Datasets ◽  
Variant Protein ◽  
Novel Protein

We have implemented the pypgatk package and the pgdb workflow to create proteogenomics databases based on ENSEMBL re-sources. The tools allow the generation of protein sequences from novel protein-coding transcripts by performing a three-frame trans-lation of pseudogenes, lncRNAs, and other non-canonical transcripts, such as those produced by alternative splicing events. It also includes exonic out-of-frame translation from otherwise canonical protein-coding mRNAs. Moreover, the tool enables the generation of variant protein sequences from multiple sources of genomic variants including COSMIC, cBioportal, gnomAD, and mutations de-tected from sequencing of patient samples. pypgatk and pgdb provide multiple functionalities for database handling, notably optimized target/decoy generation by the algorithm DecoyPyrat. Finally, we perform a reanalysis of four public datasets in PRIDE by generating cell-type specific databases for 65 cell lines using the pypgatk and pgdb workflow, revealing a wealth of non-canonical or cryptic peptides amounting to more than 10% of the total number of peptides identified (43,501 out of 402,512).

scholarly journals In vivo single-cell profiling of lncRNAs during Ebola virus infection

2022 ◽  
Author(s):  
Luisa Santus ◽  
Raquel García-Pérez ◽  
Maria Sopena-Rios ◽  
Aaron E Lin ◽  
Gordon C Adams ◽  
...  
Keyword(s):  
Viral Infection ◽  
Single Cell ◽  
Ebola Virus ◽  
Cell Type ◽  
Protein Coding ◽  
Expression Variation ◽  
Lncrna Expression ◽  
Ebov Infection ◽  
Cell Type Specific

Long non-coding RNAs (lncRNAs) are pivotal mediators of systemic immune response to viral infection, yet most studies concerning their expression and functions upon immune stimulation are limited to in vitro bulk cell populations. This strongly constrains our understanding of how lncRNA expression varies at single-cell resolution, and how their cell-type specific immune regulatory roles may differ compared to protein-coding genes. Here, we perform the first in-depth characterization of lncRNA expression variation at single-cell resolution during Ebola virus (EBOV) infection in vivo. Using bulk RNA-sequencing from 119 samples and 12 tissue types, we significantly expand the current macaque lncRNA annotation. We then profile lncRNA expression variation in immune circulating single-cells during EBOV infection and find that lncRNAs' expression in fewer cells is a major differentiating factor from their protein-coding gene counterparts. Upon EBOV infection, lncRNAs present dynamic and mostly cell-type specific changes in their expression profiles especially in monocytes, the main cell type targeted by EBOV. Such changes are associated with gene regulatory modules related to important innate immune responses such as interferon response and purine metabolism. Within infected cells, several lncRNAs have positively and negatively correlated expression with viral load, suggesting that expression of some of these lncRNAs might be directly hijacked by EBOV to attack host cells. This study provides novel insights into the roles that lncRNAs play in the host response to acute viral infection and paves the way for future lncRNA studies at single-cell resolution.

scholarly journals Neuronal cell-type-specific alternative splicing: A mechanism for specifying connections in the brain?

Neurogenesis ◽  
2015 ◽  
Vol 2 (1) ◽  
pp. e1122699 ◽  
Author(s):  
Joshua Shing Shun Li ◽  
Grace Ji-eun Shin ◽  
S Sean Millard
Keyword(s):  
Alternative Splicing ◽  
Neuronal Cell ◽  
Cell Type ◽  
Specific Alternative ◽  
Cell Type Specific ◽  
The Brain

scholarly journals Post-transcriptional control of cellular differentiation by the RNA exosome complex

2020 ◽  
Vol 48 (21) ◽  
pp. 11913-11928
Author(s):  
Isabela Fraga de Andrade ◽  
Charu Mehta ◽  
Emery H Bresnick
Keyword(s):  
Cellular Differentiation ◽  
Transcriptional Control ◽  
Cell Type ◽  
Protein Coding ◽  
Regulatory Machinery ◽  
Regulatory Complex ◽  
Cell Type Specific ◽  
Rna Exosome ◽  
Post Transcriptional Regulation ◽  
Exosome Complex

Abstract Given the complexity of intracellular RNA ensembles and vast phenotypic remodeling intrinsic to cellular differentiation, it is instructive to consider the role of RNA regulatory machinery in controlling differentiation. Dynamic post-transcriptional regulation of protein-coding and non-coding transcripts is vital for establishing and maintaining proteomes that enable or oppose differentiation. By contrast to extensively studied transcriptional mechanisms governing differentiation, many questions remain unanswered regarding the involvement of post-transcriptional mechanisms. Through its catalytic activity to selectively process or degrade RNAs, the RNA exosome complex dictates the levels of RNAs comprising multiple RNA classes, thereby regulating chromatin structure, gene expression and differentiation. Although the RNA exosome would be expected to control diverse biological processes, studies to elucidate its biological functions and how it integrates into, or functions in parallel with, cell type-specific transcriptional mechanisms are in their infancy. Mechanistic analyses have demonstrated that the RNA exosome confers expression of a differentiation regulatory receptor tyrosine kinase, downregulates the telomerase RNA component TERC, confers genomic stability and promotes DNA repair, which have considerable physiological and pathological implications. In this review, we address how a broadly operational RNA regulatory complex interfaces with cell type-specific machinery to control cellular differentiation.

scholarly journals Dynamic Antagonism between ETR-3 and PTB Regulates Cell Type-Specific Alternative Splicing

2002 ◽  
Vol 9 (3) ◽  
pp. 649-658 ◽  
Author(s):  
Nicolas Charlet-B ◽  
Gopal Singh ◽  
Thomas A. Cooper ◽  
Penny Logan
Keyword(s):  
Alternative Splicing ◽  
Cell Type ◽  
Specific Alternative ◽  
Cell Type Specific

scholarly journals Activation-Dependent TRAF3 Exon 8 Alternative Splicing Is Controlled by CELF2 and hnRNP C Binding to an Upstream Intronic Element

2016 ◽  
Vol 37 (7) ◽  
Author(s):  
Astrid-Solveig Schultz ◽  
Marco Preussner ◽  
Mario Bunse ◽  
Rotem Karni ◽  
Florian Heyd
Keyword(s):  
Alternative Splicing ◽  
Exon Skipping ◽  
Regulatory Elements ◽  
Model Systems ◽  
Regulatory Sequence ◽  
Dependent Manner ◽  
Cell Type ◽  
Activated T Cells ◽  
Hnrnp C ◽  
Cell Type Specific

ABSTRACT Cell-type-specific and inducible alternative splicing has a fundamental impact on regulating gene expression and cellular function in a variety of settings, including activation and differentiation. We have recently shown that activation-induced skipping of TRAF3 exon 8 activates noncanonical NF-κB signaling upon T cell stimulation, but the regulatory basis for this splicing event remains unknown. Here we identify cis- and trans-regulatory elements rendering this splicing switch activation dependent and cell type specific. The cis-acting element is located 340 to 440 nucleotides upstream of the regulated exon and acts in a distance-dependent manner, since altering the location reduces its activity. A small interfering RNA screen, followed by cross-link immunoprecipitation and mutational analyses, identified CELF2 and hnRNP C as trans-acting factors that directly bind the regulatory sequence and together mediate increased exon skipping in activated T cells. CELF2 expression levels correlate with TRAF3 exon skipping in several model systems, suggesting that CELF2 is the decisive factor, with hnRNP C being necessary but not sufficient. These data suggest an interplay between CELF2 and hnRNP C as the mechanistic basis for activation-dependent alternative splicing of TRAF3 exon 8 and additional exons and uncover an intronic splicing silencer whose full activity depends on the precise location more than 300 nucleotides upstream of the regulated exon.

scholarly journals Evaluating the contribution of cell-type specific alternative splicing to variation in lipid levels

2019 ◽  
Author(s):  
K.A.B. Gawronski ◽  
W. Bone ◽  
Y. Park ◽  
E. Pashos ◽  
X. Wang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Quantitative Trait ◽  
Cell Types ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Lipid Levels ◽  
Cell Type ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
Cell Type Specific

AbstractBackgroundGenome-wide association studies have identified 150+ loci associated with lipid levels. However, the genetic mechanisms underlying most of these loci are not well-understood. Recent work indicates that changes in the abundance of alternatively spliced transcripts contributes to complex trait variation. Consequently, identifying genetic loci that associate with alternative splicing in disease-relevant cell types and determining the degree to which these loci are informative for lipid biology is of broad interest.Methods and ResultsWe analyze gene splicing in 83 sample-matched induced pluripotent stem cell (iPSC) and hepatocyte-like cell (HLC) lines (n=166), as well as in an independent collection of primary liver tissues (n=96). We observe that transcript splicing is highly cell-type specific, and the genes that are differentially spliced between iPSCs and HLCs are enriched for metabolism pathway annotations. We identify 1,381 HLC splicing quantitative trait loci (sQTLs) and 1,462 iPSC sQTLs and find that sQTLs are often shared across cell types. To evaluate the contribution of sQTLs to variation in lipid levels, we conduct colocalization analysis using lipid genome-wide association data. We identify 19 lipid-associated loci that colocalize either with an HLC expression quantitative trait locus (eQTL) or sQTL. Only one locus colocalizes with both an sQTL and eQTL, indicating that sQTLs contribute information about GWAS loci that cannot be obtained by analysis of steady-state gene expression alone.ConclusionsThese results provide an important foundation for future efforts that use iPSC and iPSC-derived cells to evaluate genetic mechanisms influencing both cardiovascular disease risk and complex traits in general.

scholarly journals Cis-regulatory elements of the mitotic regulator, string/Cdc25

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1793-1803 ◽  
Author(s):  
D.A. Lehman ◽  
B. Patterson ◽  
L.A. Johnston ◽  
T. Balzer ◽  
J.S. Britton ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Cell Type ◽  
Protein Coding ◽  
Cis Acting ◽  
Mitotic Kinase ◽  
Cell Type Specific ◽  
Simple Growth ◽  
Drosophila Cells ◽  
Specific Control ◽  
Control String

Mitosis in most Drosophila cells is triggered by brief bursts of transcription of string (stg), a Cdc25-type phosphatase that activates the mitotic kinase, Cdk1 (Cdc2). To understand how string transcription is regulated, we analyzed the expression of string-lacZ reporter genes covering approximately 40 kb of the string locus. We also tested protein coding fragments of the string locus of 6 kb to 31.6 kb for their ability to complement loss of string function in embryos and imaginal discs. A plethora of cis-acting elements spread over >30 kb control string transcription in different cells and tissue types. Regulatory elements specific to subsets of epidermal cells, mesoderm, trachea and nurse cells were identified, but the majority of the string locus appears to be devoted to controlling cell proliferation during neurogenesis. Consistent with this, compact promotor-proximal sequences are sufficient for string function during imaginal disc growth, but additional distal elements are required for the development of neural structures in the eye, wing, leg and notum. We suggest that, during evolution, cell-type-specific control elements were acquired by a simple growth-regulated promoter as a means of coordinating cell division with developmental processes, particularly neurogenesis.

Sign in / Sign up

Export Citation Format

Share Document