Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Hidden Proteome Encoded by circRNAs in Human Placentas: Implications for Uncovering Preeclampsia Pathogenesis

ABSTRACT: Circular RNAs (circRNAs) are consistently overlooked as translational templates due to computational and experimental limitations. Here, we used multi-omics approaches to identify new translational events of circRNAs in human placentas, and assessed the roles of circRNA-encoded proteins in placentation and associated disorders based on the recently proposed protein bait hypothesis. The combination of placental circRNA sequencing and bioinformatics analysis revealed 219607 circRNAs, of which 35% were identified by the Coding Potential Assessment Tool (CPAT) as having >50% coding probability. Ribosomal profiling further identified 528 novel coding circRNAs, including 217 that coded for microproteins verified by LC-MS/MS. Based on these data, we established the Placental Microprotein Bank (PMB) for coding circRNAs and their coded proteins. These proteins have lower molecular weights, higher stable indices and hydrophobicity compared to the canonical proteins, and potentially link to placental development and adverse pregnancy outcomes such as pre-eclampsia. Furthermore, we identified circPRKCB119aa as a novel preeclampsia-related microprotein that enhanced trophoblast autophagy by inhibiting phosphorylation of its cognate linear-spliced isoform protein kinase C (PKC) β. In summary, we discovered a hidden circRNA-encoded proteome in the human placenta, which offers new insights into the mechanisms underlying placentation and its disorders such as, but not limited to, preeclampsia.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196032 | GEO | 2022/02/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Structured elements drive circular RNA translation and expand the human proteome part2

Project description:The human genome encodes tens of thousands circular RNAs (circRNAs) whose levels correlate with many disease states. While studies have focused on the non-coding functions of circRNAs, emerging evidence suggests that a handful of circRNAs encode proteins. Translation canonically starts by recognition of mRNA 5’cap and scanning to the start codon; how circRNA translation initiates remains unclear. Here, we developed a high-throughput screen to systematically identify and quantify RNA sequences that can direct circRNA translation. We identify and validate over 17,000 circRNA internal ribosome entry sites (IRES) and reveal that 18S rRNA complementarity and a structured RNA element on the IRES are important for facilitating circRNA cap-independent translation. With genomic and peptidomic analyses of the IRES, we identified nearly 1,000 putative endogenous protein-coding circRNAs and hundreds of translational units encoded by these circRNAs. We further characterized circFGFR1p, a protein encoded by circFGFR1, functions as a negative regulator of FGFR1 to suppress cell growth under stress conditions. The circRNA proteome may be important links among circRNA, biological control, and disease.

2021-08-23 | PXD025235 | Pride

Structured elements drive circular RNA translation and expand the human proteome, part4

2021-08-26 | PXD025203 | Pride

Structured elements drive circular RNA translation and expand the human proteome, part3

Project description:The human genome encodes tens of thousands circular RNAs (circRNAs) whose levels correlate with many disease states. While studies have focused on the non-coding functions of circRNAs, emerging evidence suggests that a handful of circRNAs encode proteins. Translation canonically starts by recognition of mRNA 5â€™cap and scanning to the start codon; how circRNA translation initiates remains unclear. Here, we developed a high-throughput screen to systematically identify and quantify RNA sequences that can direct circRNA translation. We identify and validate over 17,000 circRNA internal ribosome entry sites (IRES) and reveal that 18S rRNA complementarity and a structured RNA element on the IRES are important for facilitating circRNA cap-independent translation. With genomic and peptidomic analyses of the IRES, we identified nearly 1,000 putative endogenous protein-coding circRNAs and hundreds of translational units encoded by these circRNAs. We further characterized circFGFR1p, a protein encoded by circFGFR1, functions as a negative regulator of FGFR1 to suppress cell growth under stress conditions. The circRNA proteome may be important links among circRNA, biological control, and disease.

2021-08-25 | PXD025233 | Pride

Structured elements drive circular RNA translation and expand the human proteome, part1

2021-08-23 | PXD024993 | Pride

Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides

Project description:Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5’ cap and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed circRNAs in human cancers could be an unexplored source of tumor-specific antigens, potentially mediating anti-tumor T cell responses. This study presents an immunopeptidomics workflow with a specific focus on generating a circRNA-specific protein fasta reference. The main goal of this workflow is to streamline the process of identifying and validating human leukocyte antigen (HLA) bound peptides potentially originating from circRNAs. We increased the analytical stringency of our workflow by retaining peptides identified independently by two mass spectrometry search engines and/or by applying a group-specific FDR for canonical-derived and circRNA-derived peptides. A subset of circRNA-derived peptides specifically encoded by the region spanning the back-splice junction (BSJ) were validated with targeted MS, and with direct Sanger sequencing of the respective source transcripts. Our workflow identified 54 unique BSJ-spanning circRNA-derived peptides in the immunopeptidome of melanoma and lung cancer samples. Our novel approach enlarges the catalog of source proteins that can be explored for immunotherapy.

2024-03-20 | PXD043989 | Pride

Circular RNA microarray expression profile in preeclampsia and natural pregnancy placenta tissues

Project description:To determine the circRNA expression profile in preeclampsia and natural pregnancy placenta tissues, we uesed circRNA microArray analysis form Arraystar to examine the expression of circRNAs in preeclampsia and natural pregnancy placenta tissues.

2022-03-23 | GSE137854 | GEO

circRNA expression and characterization in multiple sclerosis patients and controls

Project description:Circular RNAs (circRNAs) are a class of non-coding RNAs increasingly emerging as crucial actors in the pathogenesis and progression of human diseases, including autoimmune and neurological disorders as multiple sclerosis (MS). We performed RNA-seq experiments on circRNA-enriched samples, derived from peripheral blood mononuclear cells of 10 MS patients and 10 matched controls. We detected 5,663 circRNAs, and expression analysis revealed 166 differentially expressed circRNAs in MS patients.

2022-12-01 | GSE161196 | GEO

Different expression profiles of miRNAs in preeclampsia and normal placenta (miRNA)

Project description:Preeclampsia is usually considered as a placental basis of diseases, as there are many differently expressed proteins or pathogenic proteins expressed in the placenta. Owing to the important role of post-transcriptional gene regulation in phenotypes and functions of cells, non-coding ribonucleic acid (ncRNA) molecules contributed to the regulation. We collected 7 placental samples from 3 preeclampsia patients and 4 normal women, focused on the basal plate of placenta, as it is the direct connection of mother and fetal, and adopted SBC human ceRNA array V1.0（4×180K）and human miRNA microarray (8*60 K). The results revealed that expressions of 2840 lncRNAs, 1093 mRNAs, 4282 circRNAs and 4 miRNAs were different between preeclampsia and normal placentas. The functions of differentially expressed lncRNAs and co-expressed potential targeting genes were predicted by analyzing Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis. Furthermore, we analyzed and find the co-expression and interaction patterns of different RNAs and possible ceRNA mechanism. The present study provided a systematic perspective on the potential function of non-coding RNAs (ncRNAs) in the pathogenesis of preeclampsia.

2018-03-01 | GSE96983 | GEO

Different expression profiles of lncRNAs, mRNAs and circRNAs in preeclampsia and normal placenta (ceRNA)

2018-03-01 | GSE96984 | GEO

RNA-seq reveals differentially expressed lncRNAs and circRNAs and their associated functional network in HTR-8/Svneo cells under hypoxic conditions

Project description:Placental hypoxia is hazardous to maternal health as well as fetal growth and development. Preeclampsia and intrauterine growth restriction are common pregnancy problems, and one of the causes is placental hypoxia.Placental hypoxia is linked to a number of pregnancy illnessesv. To investigate their potential function in anoxic circumstances, we mimicked the anoxic environment of HTR-8/Svneo cells and performed lncRNA and circRNA studies on anoxic HTR-8/Svneo cells using high-throughput RNA sequencing. The miRNA target genes were predicted by integrating the aberrant expression of miRNAs in the placenta of preeclampsia and intrauterine growth restriction, and a ceRNA network map was developed to conduct a complete transcriptomic and bioinformatics investigation of circRNAs and lncRNAs. The signaling pathways in which the genes were primarily engaged were predicted using GO and KEGG analyses. To propose a novel explanation for trophoblastic organism failure caused by lncRNAs and circRNAs in an anoxic environment.

2023-12-06 | GSE248957 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data