Possible effect of hyperthermia on accessibility of cellular and viral miRNAs to mRNAs involved in HIV replication.

MORANDO N; GUZMAN L; RABINOVICH D; PANDO MA

Bernal

Congreso; II Reunión Argentina de Biología de ARNs no codificantes.; 2018

Universidad Nacional de Quilmes

Introduction: The relationship between HIV and cocaine is multifactorial and involves changes in the expression patterns of cellular and viral-encoded miRNAs involved in HIV replication. Cocaine can induce hyperthermia up to 430C. This suggests a possible indirect effect of cocaine on miRNA-mediated HIV regulation, given that changes in temperature can affect mRNA secondary structure altering the accessibility of miRNA to its binding site. The objective of the study was to perform an in silico analysis of the effect of temperature on binding sites of miRNAs able to affect HIV replication. Methods: Cellular and viral-encoded miRNAs involved in HIV replication, with cellular or viral mRNA targets, were identified from the literature. Sequences of these miRNAs were obtained from the miRBase database and the target sites within the corresponding mRNAs were identified using BiBiserv 2 (RNAhybrid). mRNA secondary structures at 370C and 430C, with their corresponding free energy (∆G) values, were predicted using UNAFOLD (mFold2.3). For each temperature, the difference in ∆G (∆∆G) between the most stable structure (where the bases at the miRNA binding site tend to be paired) and the structure where all of these bases are unpaired was calculated. Results: 48 miRNA-mRNA pairs were analyzed, including 22 cellular miRNA-viral mRNA pairs, 22 cellular miRNA-cellular mRNA pairs, 3 viral miRNA-viral mRNA pairs and 1 viral miRNA-viral mRNA pair. In 46 cases a rise in temperature was predicted to lower the ∆∆G, which would imply higher accessibility to the target site. When considering only the bases within the seed region (those most critical for effective miRNA binding), this same effect was observed in 35 pairs. When comparing the 430C structure with respect to the 370C structure, changes in the pattern of paired nucleotides at the miRNA binding site were observed in 14 cases: 1 case with no net change, 7 cases with a higher number and 6 cases with a lower number of paired nucleotides. Conclusion: In silico analyses suggest that changes in temperature can alter miRNA access to mRNAs involved in HIV replication. This could be relevant for patients with HIV who use substances that cause hyperthermia.