The role of SRP9/SRP14 in regulating Alu RNA

Abstract

There are over 1 million Alu elements in the human genome which have the potential to be transcribed into discrete, non-coding Alu RNAs. Alu RNAs are involved in a myriad of biological diseases and are thought to interact with the protein heterodimer SRP9/SRP14. Although 99% of Alu RNAs are unique, most research has been focused on the signal recognition particle RNA and its interaction with SRP9/SRP14. In this project, SRP9/SRP14 is established as a transcriptional regulator of both the signal recognition particle RNA, and another abundant Alu RNA, brain cytoplasmic RNA 1 (BC200). In this study, the association of SRP9/SRP14 to the Alu genetic loci was observed independently of transcription, and a model of SRP9/SRP14 co-transcriptionally regulating Alu RNA was proposed. Following this, minor mutations to the BC200 Alu domain were revealed to significantly decrease expression. Structural characterization and modelling of the BC200 Alu domain and the low expression mutant demonstrated both RNA possess canonical Alu RNA fold. A recently discovered short human Alu RNA was found to have a unique Alu RNA fold and lacked association with SRP9/SRP14. Ribonucleoprotein immunoprecipitation followed by sequencing of SRP9 and SRP14 was also used to identify 21 novel non-coding Alu RNA. Together, this project demonstrated the significance of SRP9/SRP14 in modulating Alu RNA expression, while highlighting the structural diversity and sequence variability of Alu RNA.