17 April 2023

The yellow fever mosquito Aedes aegypti transmits viruses such as the dengue and zika viruses that cause debilitating diseases in humans. Small, non-coding RNAs are essential for gene regulation, genome integrity, and antiviral immunity in Aedes mosquitoes, as they are in other animals. Yet, small RNA biology in mosquitoes is more complex than in most other organisms, due to extensive duplication of a class of genes that encode so-called PIWI proteins. Functions of the PIWI proteins and their associated PIWI-interacting RNAs (piRNAs) are beginning to be elucidated, but how piRNAs are made has thus far been unclear.

Researcher Jieqiong Qu and colleagues in the research group of Ronald van Rij set out to characterize the regions in the Aedes aegypti genome that encode piRNAs. Their results were recently published in the journal Cell Reports.

piRNAs are encoded in dedicated regions of the genome called piRNA clusters. The researchers used a combination of transcriptome and chromatin state analyses to study regulatory elements in the genome of Aedes mosquitoes. Unexpectedly, piRNA clusters did not have chromatin marks associated with promoter elements at which transcription starts. Instead, the researchers found that transcription starts at the promoters of nearly upstream genes, but fails to stop at normal termination sites, resulting in transcripts that cover the piRNA cluster. They propose that these unusually long transcripts are processed into piRNAs.

The researchers next compared piRNA clusters of Aedes aegypti with those of the Asian tiger mosquito Aedes albopictus and found that similar upstream genes drive piRNA expression in both mosquito species. Unexpectedly, the sequences of the piRNA clusters themselves differed dramatically. Specifically, piRNA clusters in both species were enriched for fragments of viral sequences (called endogenous viral elements), but the specific viral sequences differed between the mosquito species. The researchers propose that piRNA clusters function as ‘traps’ for viral sequences and that the piRNAs made from these sequences protect the mosquito from subsequent challenges with the same viruses.

 

Read the study here

Qu J, Betting V, van Iterson R, Kwaschik FM, van Rij RP. Chromatin profiling identifies transcriptional readthrough as a conserved mechanism for piRNA biogenesis in mosquitoes Cell Reports. 2023; 42(3):112257. doi: 10.1016/j.celrep.2023.112257. 

Related news items