A secondary structure within a human piRNA modulates its functionality.

A secondary structure within a human piRNA modulates its functionality. Biochimie. 2018 Nov 08;: Authors: Balaratnam S, Hettiarachchilage M, West N, Piontkivska H, Basu S Abstract The piwi interacting RNAs (piRNAs) are small non-coding RNAs, mostly 24-32 nucleotides in length. The piRNAs are not known to have any conserved secondary structure or sequence motifs. Using bioinformatics analysis, we discovered the presence of putative G-quadruplex (GQ) forming sequences in human piRNAs. We studied human piR-48164/piR-GQ containing potential GQ forming sequence and using biochemical and biophysical techniques confirmed its ability to form a GQ. Using EMSA, we discovered that formation of GQ structure led to inhibition of the piRNA binding to HIWI-PAZ domain as well as complementary base pairing to a target RNA. The inability of the piR-GQ to interact with the PIWI protein might be detrimental to the function of the piRNA. To investigate if the formation of GQ structure in piRNA prevents its target gene silencing in vivo, we used a reporter assay. The piR-GQ failed to inhibit the reporter gene expression while a mutated version that lacked the ability to form GQ inhibited reporter gene expression indicating that the presence of GQ in piRNA is detrimental to its function. These studies unraveled the dependence of a piRNA's functionality on an RNA secondary structure and added a new layer of regulation to their function. PMID: 304148...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research