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Roles of microRNAs and long‐noncoding RNAs in human immunodeficiency virus replication

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MicroRNAs (miRNAs) and long‐noncoding RNAs (lncRNAs) are involved in many biological processes, including viral replication. In this review, the role of miRNAs and lncRNAs in human immunodeficiency virus (HIV) replication will be discussed. The review focuses on miRNAs that target cellular proteins involved in HIV replication—proteins that mediate steps in the viral life cycle, as well as proteins of the innate immune system that inhibit HIV replication. Given the large number of miRNAs encoded in the human genome, as well as the large number of cellular proteins involved in HIV replication, the number of miRNAs identified to date that affect viral replication are certainly only the ‘tip of the iceberg’. The review also discusses two lncRNAs that are involved in HIV gene regulation—7SK RNA and NEAT1 RNA. 7SK RNA is involved in HIV Tat protein stimulation of RNA polymerase II elongation of the integrated provirus, while NEAT1 RNA is involved in HIV Rev protein export of incompletely spliced viral transcripts. WIREs RNA 2015, 6:661–670. doi: 10.1002/wrna.1308 This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes RNA Export and Localization > Nuclear Export/Import Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease
Steps in human immunodeficiency virus (HIV) replication cycle regulated by cellular microRNAs (miRNAs). Steps in the viral replication cycle are numbered. The miRNAs that inhibit replication are shown in red and their cellular targets that promote replication are shown in green. The miRNAs that enhance viral replication are shown in green and their cellular targets (antiviral proteins) are shown in red.
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Model for role of NEAT1 RNA and paraspeckles in human immunodeficiency virus (HIV) Rev function. (1) NEAT1 RNA is required for the formation of paraspeckle structures in the nucleus. PSF, p54nrb, and RBM14 are protein components of paraspeckles, and unspliced HIV transcripts are sequestered in paraspeckles through binding to PSF, p54nrb, and RBM14. (2) The association of RBM14 with CRM1 allows Rev/CRM1 to recruit unspliced viral transcripts to the nucleolus. (3) A nuclear export complex containing Rev/CRM1/RAN‐GTP are bound to unspliced viral transcripts, and this complex traffics through nuclear pores to the cytoplasm. (4) The hydrolysis of RAN‐GTP to RAN‐GDP results in the releases of viral transcripts in the cytoplasm.
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Model for role of 7SK RNP in human immunodeficiency virus (HIV) Tat function. (1) Cyclin T1/CDK9 are sequestered in the 7SK RNP in a catalytic inactive form. (2) Cyclin T1/CDK9 may be extracted from the 7SK RNP by Tat and this trimeric complex binds to TAR RNA formed at the 5′ end of the nascent viral transcripts. Alternatively, the 7SK RNP may bind to the 5′ LTR, and Cyclin T1/CDK9 are then extracted from the RNP when TAR RNA is synthesized. (3) Upon binding to TAR RNA, CDK9 in the Cyclin T1/CDK9/Tat complex phosphorylate several substrates in the RNA polymerase II complex, resulting in activation of transcriptional elongation.
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RNA Export and Localization > Nuclear Export/Import
RNA in Disease and Development > RNA in Disease
Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs
RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes

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