Topic
RNA
About: RNA is a research topic. Over the lifetime, 111695 publications have been published within this topic receiving 5475262 citations. The topic is also known as: ribonucleic acid.
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City of Hope National Medical Center1, University of Cincinnati Academic Health Center2, Sun Yat-sen University3, University of Chicago4, Howard Hughes Medical Institute5, China Medical University (PRC)6, Cincinnati Children's Hospital Medical Center7, Martin Luther University of Halle-Wittenberg8, Zhejiang University9
TL;DR: This work reports the insulin-like growth factor 2 mRNA-binding proteins as a distinct family of m6A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6A)C sequence, and identifies IGF2BPs as an additional class of N6-methyladenosine (m 6A) reader proteins.
Abstract: N6-methyladenosine (m6A) is the most prevalent modification in eukaryotic messenger RNAs (mRNAs) and is interpreted by its readers, such as YTH domain-containing proteins, to regulate mRNA fate. Here, we report the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; including IGF2BP1/2/3) as a distinct family of m6A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6A)C sequence. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Moreover, the K homology domains of IGF2BPs are required for their recognition of m6A and are critical for their oncogenic functions. Thus, our work reveals a different facet of the m6A-reading process that promotes mRNA stability and translation, and highlights the functional importance of IGF2BPs as m6A readers in post-transcriptional gene regulation and cancer biology.
1,373 citations
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TL;DR: Using the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system, this article constructed a genome-wide single-guide RNA library to screen for genes required for proliferation and survival in a human cancer cell line.
Abstract: Large-scale genetic analysis of lethal phenotypes has elucidated the molecular underpinnings of many biological processes. Using the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system, we constructed a genome-wide single-guide RNA library to screen for genes required for proliferation and survival in a human cancer cell line. Our screen revealed the set of cell-essential genes, which was validated with an orthogonal gene-trap-based screen and comparison with yeast gene knockouts. This set is enriched for genes that encode components of fundamental pathways, are expressed at high levels, and contain few inactivating polymorphisms in the human population. We also uncovered a large group of uncharacterized genes involved in RNA processing, a number of whose products localize to the nucleolus. Last, screens in additional cell lines showed a high degree of overlap in gene essentiality but also revealed differences specific to each cell line and cancer type that reflect the developmental origin, oncogenic drivers, paralogous gene expression pattern, and chromosomal structure of each line. These results demonstrate the power of CRISPR-based screens and suggest a general strategy for identifying liabilities in cancer cells.
1,371 citations
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18 Mar 1994TL;DR: The polynucleotide sequences, comprising DNA and RNA molecules, can be directly administered, for example by injection, to tissues, such as muscle, and expressed as a protein, polypeptide or polyptide.
Abstract: Polynucleotide sequences, comprising DNA and RNA molecules can be directly administered, for example by injection, to tissues, such as muscle, and expressed as a protein, polypeptide or polypeptide. The polynucleotides can be contained within liposomes or the polynucleotides can free from association with transfection-facilitating proteins, viral particles, liposomal formulations, charged lipids and calcium phosphate precipitating agents.
1,370 citations
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TL;DR: It is shown by gene targeting that RIG-I is essential for induction of type I interferons (IFNs) after infection with RNA viruses in fibroblasts and conventional dendritic cells (DCs) and exert antiviral responses in a cell type-specific manner.
1,370 citations
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TL;DR: It is shown that a short interfering RNA (siRNA) can repress expression of a target mRNA with partially complementary binding sites in its 3' UTR, much like the demonstrated function of endogenously encoded microRNAs (miRNAs).
Abstract: With the discovery of RNA interference (RNAi) and related phenomena, new regulatory roles attributed to RNA continue to emerge. Here we show, in mammalian tissue culture, that a short interfering RNA (siRNA) can repress expression of a target mRNA with partially complementary binding sites in its 3′ UTR, much like the demonstrated function of endogenously encoded microRNAs (miRNAs). The mechanism for this repression is cooperative, distinct from the catalytic mechanism of mRNA cleavage by siRNAs. The use of siRNAs to study translational repression holds promise for dissecting the sequence and structural determinants and general mechanism of gene repression by miRNAs.
1,370 citations