Dataset Information

Translating the Untranslated Region.

ABSTRACT: Gene expression programs undergo constant regulation to quickly adjust to environmental stimuli that alter the physiological status of the cell, like cellular stress or infection. Gene expression is tightly regulated by multilayered regulatory elements acting in both cis and trans. Posttranscriptional regulation of the 3' untranslated region (UTR) is a powerful regulatory process that determines the rate of protein translation from mRNA. Regulatory elements targeting the 3' UTR include microRNAs, RNA-binding proteins, and long noncoding RNAs, which dramatically alter the immune response. We provide an overview of our current understanding of posttranscriptional regulation of immune gene expression. The focus of this review is on regulatory elements that target the 3' UTR. We delineate how the synergistic or antagonistic interactions of posttranscriptional regulators determine gene expression levels and how dysregulation of 3' UTR-mediated posttranscriptional control associates with human diseases.

SUBMITTER: Schwerk J

PROVIDER: S-EPMC4648541 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Translating the Untranslated Region.

Schwerk Johannes J Savan Ram R

Journal of immunology (Baltimore, Md. : 1950) 20151001 7

Gene expression programs undergo constant regulation to quickly adjust to environmental stimuli that alter the physiological status of the cell, like cellular stress or infection. Gene expression is tightly regulated by multilayered regulatory elements acting in both cis and trans. Posttranscriptional regulation of the 3' untranslated region (UTR) is a powerful regulatory process that determines the rate of protein translation from mRNA. Regulatory elements targeting the 3' UTR include microRNAs ...[more]

PMID: 26386038

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Project description:Enteroviral RNA genomes share a long, highly structured 5' untranslated region (5' UTR) containing a type I internal ribosome entry site (IRES). The 5' UTR is composed of stably folded RNA domains connected by unstructured RNA regions. Proper folding and functioning of the 5' UTR underlies the efficiency of viral replication and also determines viral virulence. We have characterized the structure of 5' UTR genomic RNA from coxsackievirus B3 using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) and base-specific chemical probes in solution. Our results revealed novel structural features, including realignment of major domains, newly identified long-range interactions, and an intrinsically disordered connecting region. Together, these newly identified features contribute to a model for enteroviral 5' UTRs with type I IRES elements that links structure to function during the hierarchical processes directed by genomic RNA during viral infection.IMPORTANCE Enterovirus infections are responsible for human diseases, including myocarditis, pancreatitis, acute flaccid paralysis, and poliomyelitis. The virulence of these viruses depends on efficient recognition of the RNA genome by a large family of host proteins and protein synthesis factors, which in turn relies on the three-dimensional folding of the first 750 nucleotides of the molecule. Structural information about this region of the genome, called the 5' untranslated region (5' UTR), is needed to assist in the process of vaccine and antiviral development. This work presents a model for the structure of the enteroviral 5' UTR. The model includes an RNA element called an intrinsically disordered RNA region (IDRR). Intrinsically disordered proteins (IDPs) are well known, but correlates in RNA have not been proposed. The proposed IDRR is a 20-nucleotide region, long known for its functional importance, where structural flexibility helps explain recognition by factors controlling multiple functional states.

Dataset Information

Translating the Untranslated Region.

Publications

Translating the Untranslated Region.

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