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.

C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins.

Abstract: An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. A fundamental question is whether toxicity is driven by the repeat RNA itself and/or by dipeptide repeat proteins generated by repeat-associated, non-ATG translation. To address this question, we developed in vitro and in vivo models to dissect repeat RNA and dipeptide repeat protein toxicity. Expression of pure repeats, but not stop codon-interrupted "RNA-only" repeats in Drosophila caused adult-onset neurodegeneration. Thus, expanded repeats promoted neurodegeneration through dipeptide repeat proteins. Expression of individual dipeptide repeat proteins with a non-GGGGCC RNA sequence revealed that both poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. These findings are consistent with a dual toxicity mechanism, whereby both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration.

Unprecedented genomic diversity of RNA viruses in arthropods reveals the ancestry of negative-sense RNA viruses

Abstract: Many illnesses, including influenza, hemorrhagic fever, and rabies, are caused by a group of viruses called negative-sense RNA viruses. The genetic information—or genome—of these viruses is encoded in strands of RNA that must be copied before they can be translated into the proteins needed to build new viruses. It is currently known that there are at least eight different families of these viruses, which have a wide range of shapes and sizes and arrange their RNA in different ways. Insects, spiders, and other arthropods carry many different RNA viruses. Many of these viruses have not previously been studied, and those that have been studied so far are mainly those that cause diseases in humans and other vertebrates. Researchers therefore only know a limited amount about the diversity of the negative-sense RNA viruses that arthropods harbor and how these viruses evolved. Studying how viruses evolve helps scientists to understand what makes some viruses deadly and others harmless and can also help develop treatments or vaccines for the diseases caused by the viruses. Li, Shi, Tian, Lin, Kang et al. collected 70 species of insects, spiders, centipedes, and other arthropods in China and sequenced all the negative-sense RNA viruses in the creatures. This revealed an enormous number of negative-sense RNA viruses, including 112 new viruses. Many of the newly discovered arthropod viruses appear to be the ancestors of disease-causing viruses, including influenza viruses and the filoviruses—the group that includes the Ebola virus. Indeed, it appears that arthropods host many—if not all—of the negative-sense RNA viruses that cause disease in vertebrates and plants. While documenting the new RNA viruses and how they are related to each other, Li et al. found many different genome structures. Some genomes were segmented, which may play an important role in evolution as segments can be easily swapped to create new genetic combinations. Non-segmented and circular genomes were also found. This genetic diversity suggests that arthropods are likely to have played a key role in the evolution of new viruses by acting as a site where many different viruses can interact and exchange genetic information.

Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box.

Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to influence the structure of hnRNA and participate in the processing of hnRNA to mRNA. The hnRNP U protein is an abundant nucleoplasmic phosphoprotein that is the largest of the major hnRNP proteins (120 kDa by SDS-PAGE). HnRNP U binds pre-mRNA in vivo and binds both RNA and ssDNA in vitro. Here we describe the cloning and sequencing of a cDNA encoding the hnRNP U protein, the determination of its amino acid sequence and the delineation of a region in this protein that confers RNA binding. The predicted amino acid sequence of hnRNP U contains 806 amino acids (88,939 Daltons), and shows no extensive homology to any known proteins. The N-terminus is rich in acidic residues and the C-terminus is glycine-rich. In addition, a glutamine-rich stretch, a putative NTP binding site and a putative nuclear localization signal are present. It could not be defined from the sequence what segment of the protein confers its RNA binding activity. We identified an RNA binding activity within the C-terminal glycine-rich 112 amino acids. This region, designated U protein glycine-rich RNA binding region (U-gly), can by itself bind RNA. Furthermore, fusion of U-gly to a heterologous bacterial protein (maltose binding protein) converts this fusion protein into an RNA binding protein. A 26 amino acid peptide within U-gly is necessary for the RNA binding activity of the U protein. Interestingly, this peptide contains a cluster of RGG repeats with characteristic spacing and this motif is found also in several other RNA binding proteins. We have termed this region the RGG box and propose that it is an RNA binding motif and a predictor of RNA binding activity.