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.
Papers published on a yearly basis
Papers
More filters
TL;DR: The results delineate the mechanism of RIG-I activation, identify CARD domains as a ubiquitin sensor, and demonstrate that unanchored K63-polyubiquitin chains are signaling molecules in antiviral innate immunity.
575 citations
TL;DR: This work found that the mRNAs of hilD (master regulator of the SPI-1 invasion genes) and flhDC (flagellar master regulator) were bound by Hfq, and presented a generic strategy that is ideal for the systems-level analysis of the post-transcriptional regulons of RNA-binding proteins and for sRNA discovery in a wide range of bacteria.
Abstract: Recent advances in high-throughput pyrosequencing (HTPS) technology now allow a thorough analysis of RNA bound to cellular proteins, and, therefore, of post-transcriptional regulons. We used HTPS to discover the Salmonella RNAs that are targeted by the common bacterial Sm-like protein, Hfq. Initial transcriptomic analysis revealed that Hfq controls the expression of almost a fifth of all Salmonella genes, including several horizontally acquired pathogenicity islands (SPI-1, -2, -4, -5), two sigma factor regulons, and the flagellar gene cascade. Subsequent HTPS analysis of 350,000 cDNAs, derived from RNA co-immunoprecipitation (coIP) with epitope-tagged Hfq or control coIP, identified 727 mRNAs that are Hfq-bound in vivo. The cDNA analysis discovered new, small noncoding RNAs (sRNAs) and more than doubled the number of sRNAs known to be expressed in Salmonella to 64; about half of these are associated with Hfq. Our analysis explained aspects of the pleiotropic effects of Hfq loss-of-function. Specifically, we found that the mRNAs of hilD (master regulator of the SPI-1 invasion genes) and flhDC (flagellar master regulator) were bound by Hfq. We predicted that defective SPI-1 secretion and flagellar phenotypes of the hfq mutant would be rescued by overexpression of HilD and FlhDC, and we proved this to be correct. The combination of epitope-tagging and HTPS of immunoprecipitated RNA detected the expression of many intergenic chromosomal regions of Salmonella. Our approach overcomes the limited availability of high-density microarrays that have impeded expression-based sRNA discovery in microorganisms. We present a generic strategy that is ideal for the systems-level analysis of the post-transcriptional regulons of RNA-binding proteins and for sRNA discovery in a wide range of bacteria.
574 citations
TL;DR: It is shown that systemic delivery of siRNAs can inhibited exogenous and endogenous gene expression in adult mice and the development of sepsis in mice following a lethal dose of lipopolysaccharide injection was significantly inhibited by pre-treatment of the animals with anti-TNF-alpha siRNA.
574 citations
TL;DR: It is demonstrated that sequences in normal human DNA homologous to the avian myc oncogene are present in multiple copies in the chromosomal DNA of the human leukaemia cell line HL-60, and this myc-related gene amplification is not present in other cultured human myeloid leukaems, including K-56214 and KG-115.
Abstract: Malignant transformation of cells by acute transforming RNA tumour viruses is mediated by the expression of certain specific pro viral DNA sequences (‘oncogenes’). These sequences have been well characterized and, in many cases, molecularly cloned1–8. These viral oncogenes are related to similar genes found in normal uninfected cells9,10. Moreover, these particular sequences are highly conserved in evolution4,11, suggesting that these genes have an important, albeit unknown, role in normal cell function. It has been suggested that an increased dosage of products of such endogenous oncogenes may be responsible for malignant transformation10,12,13. For example, increased expression of the endogenous chick c-myc oncogene has been observed in avian leukosis virus-induced transformation of chick bursal lymphocytes12. Here we demonstrate that sequences in normal human DNA homologous to the avian myc oncogene are present in multiple copies in the chromosomal DNA of the human leukaemia cell line HL-60. Other transformation-specific genes derived from the Abelson leukaemia virus4 and feline sarcoma virus6 are not amplified in HL-60. This myc-related gene amplification is not present in other cultured human myeloid leukaemia cells, including K-56214 and KG-115.
574 citations
TL;DR: It is shown that hnRNP A1 binds specifically to the primary RNA sequence pri-miR-18a before Drosha processing, which underscores a previously uncharacterized role for general RNA-binding proteins as auxiliary factors that facilitate the processing of specific miRNAs.
Abstract: hnRNP A1 is an RNA-binding protein involved in various aspects of RNA processing. Use of an in vivo cross-linking and immunoprecipitation protocol to find hnRNP A1 RNA targets resulted in the identification of a microRNA (miRNA) precursor, pre-miR-18a. This microRNA is expressed as part of a cluster of intronic RNAs, including miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92, and potentially acts as an oncogene. Here we show that hnRNP A1 binds specifically to the primary RNA sequence pri-miR-18a before Drosha processing. HeLa cells depleted of hnRNP A1 have reduced in vitro processing activity with pri-miR-18a and also show reduced abundances of endogenous pre-miR-18a. Furthermore, we show that hnRNP A1 is required for miR-18a–mediated repression of a target reporter in vivo. These results underscore a previously uncharacterized role for general RNA-binding proteins as auxiliary factors that facilitate the processing of specific miRNAs.
573 citations