Next-Generation Sequencing of Small RNAs from HIV-Infected Cells Identifies Phased microRNA Expression Patterns and Candidate Novel microRNAs Differentially Expressed upon Infection

Chang, Stewart T.; Thomas, Matthew J.; Sova, Pavel; Green, Richard R.; Palermo, Robert E.; Katze, Michael G.

Out of the five microRNAs DE at 5 hpi, three (miR-3607-5p, miR-3607-3p, and miR-3653) were significantly, negatively correlated with annotated, target mRNAs from the alternative predictions (see Table S4 ). One of these, miR-3607-3p, was highly expressed in SUP-T1 cells (see Table S4 ) and DE at all three time points (downregulated at 5 and 12 hpi and upregulated at 24 hpi), unique among the microRNAs in our study ( Fig. 2A and B) . In our analysis, miR-3607-3p showed highly significant, anticorrelated expression with 21 target mRNAs at 12 and 24 hpi (Fig. 3B ). These were enriched in annotations for "cell cycle process" and "transcriptional regulatory activity," with interleukin enhancerbinding factor 3 (ILF3) and nuclear receptor corepressor 1 (NCOR1) having both annotations. In addition, four mRNAs in this network were annotated for "transcriptional regulatory activity" and encoded transcription factors: ILF3, GABPB1 (GAbinding protein transcription factor, beta subunit 1), NFATC3 (nuclear factor of activated T cells, calcineurin-dependent 3), and TCF7 (transcription factor 7). The phased expression pattern of miR-3607-3p suggests that these targeted mRNAs may have been subjected to variable degrees of regulation-with reduced suppression early in infection and then increased suppression later in infection-during the course of HIV infection.