Abstract
Molecular chaperone networks fulfill complex roles in protein homeostasis and are essential for maintaining cell health. Hsp40s (commonly referred to as J-proteins) have critical roles in development and are associated with a variety of human diseases, yet little is known regarding the J-proteins with respect to the post-transcriptional mechanisms that regulate their expression. With relatively small alterations in their abundance and stoichiometry altering their activity, post-transcriptional regulation potentially has significant impact on the functions of J-proteins. MicroRNAs (miRNAs) are a large group of non-coding RNAs that form a complex regulatory network impacting gene expression. Here we review and investigate the current knowledge and potential intersection of miRNA regulatory networks with the J-Protein chaperone network. Analysis of datasets from the current version of TargetScan revealed a great number of predicted microRNAs targeting J-proteins compared to the limited reports of interactions to date. There are likely unstudied regulatory interactions that influence chaperone biology contained within our analysis. We go on to present some criteria for prioritizing candidate interactions including potential cooperative targeting of J-Proteins by multiple miRNAs. In summary, we offer a view on the scope of regulation of J-Proteins through miRNAs with the aim of guiding future investigations by identifying key regulatory nodes within these two complex cellular networks.
Highlights
MicroRNA networks of gene regulation and molecular chaperone networks both consist of complex webs of interactions with broad implications in shaping the proteome
Additional evidence of miRNA targeting of J-Proteins can be taken where miRNA-Argonaute protein complexes have been identified to associate with the 3’ untranslated regions (UTRs)
While the analysis identified multiple examples of potential miRNA target sequences within 8–40 nts, such as the predicted miR-217 and miR-205-5p target sequences in the 3’ UTR of the DNAJA1 mRNA, there are potential combinations of mutual exclusivity
Summary
MicroRNA (miRNA) networks of gene regulation and molecular chaperone networks both consist of complex webs of interactions with broad implications in shaping the proteome. While there have been numerous reports in the literature describing correlations of J-Protein expression with miRNA expression, there are relatively few examples where the target sequence in the 3’ UTR of the J-Protein mRNAs has been experimentally validated (see Table 1).
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