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Open AccessJournal ArticleDOI

Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types

TLDR
By deep sequencing of RNA from a variety of normal and malignant human cells, this work suggests that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.
Abstract
Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.

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Patent

Engineered nucleic acids and methods of use thereof

TL;DR: In this paper, compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression are provided. But they do not consider the use of modified messenger RNAs, which are useful to treat or prevent diseases, disorders or conditions.
Patent

Modified polynucleotides for the production of biologics and proteins associated with human disease

TL;DR: The present paper relates to the composition of polynucleotides, primary transcripts, and mmRNA molecules, and methods for their preparation, manufacture, and therapeutic use as mentioned in this paper.
Journal ArticleDOI

Circular RNAs and Cancer.

TL;DR: An in-depth study of circRNAs will provide a better understanding of carcinogenesis and assist in developing clinical diagnostic and therapeutic strategies.
Journal Article

Emerging Functions of Circular RNAs.

TL;DR: The recent progress made in understanding the biogenesis and regulation of circRNAs are highlighted, newly uncovered circRNA functions are discussed, and the methodological approaches that could reveal more exciting and unexpected roles for these RNAs are explained.
Patent

Delivery and formulation of engineered nucleic acids

TL;DR: In this paper, formulations, compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression are provided. But the methods are not suitable for the production of proteins.
References
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Journal ArticleDOI

A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

TL;DR: It is found that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role, and this analysis extended to other cancer-related genes that possess pseudogenes, and revealed a non-coding function for mRNAs.
Journal ArticleDOI

Circular transcripts of the testis-determining gene Sry in adult mouse testis

TL;DR: It is suggested that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse.
Journal ArticleDOI

Mis-splicing yields circular RNA molecules.

TL;DR: To the knowledge, this is the first case of circular transcripts being processed from nuclear pre‐mRNA in eukaryotes, and might represent a novel aspect of gene expression and hold some interesting clues about the splicing mechanism.
Journal ArticleDOI

miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA

TL;DR: This study provides the first evidence for non‐coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.
Journal ArticleDOI

Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk

TL;DR: The results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRil expression and/or structure.
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