Mapping the Small RNA Content of Simian Immunodeficiency Virions (SIV)

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Date: Sept. 23, 2013
From: PLoS ONE(Vol. 8, Issue 9)
Publisher: Public Library of Science
Document Type: Article
Length: 9,795 words
Lexile Measure: 1460L

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Within the last decade, a diverse class of non-coding RNA molecules (ncRNAs) was found to orchestrate a large number of physiological processes. The most prominent population of ncRNAs was referred to as microRNAs (miRNAs) that induce gene silencing by translational repression or mRNA decay [1]. Derived from primary transcripts, biogenesis of miRNAs starts with a precursor molecule (pri-miRNAs) that is processed by the nuclear RNase III enzyme Drosha. After nuclear export, the pre-miRNA is cleaved by the cytoplasmic RNase III enzyme Dicer that produces the mature miRNA of around 22 nt in length. To exert their function, miRNAs are incorporated into the RNA-induced silencing complex (RISC). Complementary binding of the miRNAs to its respective target transcripts then leads to mRNA degradation or translational repression, influencing physiological or promoting pathological processes. MiRNAs have been found in virtually all eukaryotic organisms. An increasing number of studies showed that miRNAs are also encoded and expressed by a variety of DNA viruses, including several members of the <named-content content-type="order" xlink:type="simple">Herpesviridae</named-content> and <named-content content-type="order" xlink:type="simple">Polyomaviridae</named-content> families (for review, see [2]). Furthermore, deep-sequencing approaches lead to the identification of short, viral-derived sequences (vsRNAs) in RNA viruses. To date, the function of these fragments in Hepatitis C-, Vesicular Stomatitis-, West Nile-, Dengue-, and Polio-virus infected cells remains unknown [3].

In addition, retroviruses, such as the human immunodeficiency virus (HIV-1), have been reported to encode miRNAs [4-7] and vsRNAs [8,9]. Retroviruses are RNA viruses that integrate in the host genome via a proviral DNA intermediate. The primary genomic RNA (gRNA) serves as mRNA and via splicing produces many subgenomic mRNAs. During the maturation of retroviral particles, a proportion of the full length RNA is packaged into progeny virions as a dimer of two identical copies. Selective packaging of this gRNA depends on the RNA-encoded Psi ([PSI]) region that is recognized by the nucleocapsid domain of the structural protein Gag [10,11]. The Gag polypeptide also binds to several cellular RNAs [12] that are selectively packaged into the virion. In HIV-1, the majority of these cellular RNAs belongs to the family of RNA polymerase III (Pol III) transcribed ncRNAs, such as tRNALys and tRNALys isoacceptors. Here, tRNALys3 anneals to the primer binding site (PBS) of the gRNA, where it serves as initiator of reverse transcription [13,14]. In addition, 7SL RNA, which is one component of the signal recognition particle (SRP) ribonucleoprotein complex, is highly enriched in HIV-1 derived virions [15]. Using mutated HIV-1 particles, there is evidence that the nucleocapsid domain of Gag mainly contributes to the selective packaging of Pol III transcribed cellular small RNAs into HIV-1 virions [16]. Recent evidence indicated that 7SL RNA could also be retained in the virion as endoribonucleolytic fragment [17]. To date, only the above mentioned cellular RNAs and RNA fragments have been identified within the virion, whereas HIV-1 encoded vsRNAs were solely detected in HIV-1 infected cells [8,18].

In this study we examined RNA packaging of the simian immunodeficiency virus (SIV mac 239) using ultra-deep sequencing technology. Our data...

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Gale Document Number: GALE|A478132810