Regulatory dynamics of B2 SINE RNAs in cellular stress and neurodegenerative contexts

Abstract

Short interspersed nuclear elements (SINEs) are abundant repetitive elements that function as transcriptional regulators during cellular stress. In mice, B2 SINE RNAs accumulate rapidly and repress RNA polymerase II. However, the mechanisms governing how B2 transcripts are processed and regulated under stress remains incompletely understood. In particular, the relationship between B2 RNA processing dynamics, and adenosine deaminase acting on RNA (ADAR) mediated adenosine to Inosine (A-I) editing has not been fully resolved. Here, an integrative experimental and computational framework was developed to investigate B2 RNA expression, processing, and A-I editing across cellular stress and neurodegenerative contexts. These analyses reveal that stress induced B2 SINE RNA accumulation is accompanied by shifts in RNA processing and A-I editing within full length transcripts. Furthermore, sense and antisense B2 transcription suggests the potential formation of double stranded RNA that may facilitate editing and influence B2 RNA processing dynamics. Together, these findings indicate that B2 SINE RNA regulation is dynamically regulated through RNA processing, A-I editing, and potential double stranded RNA formation.