SON protects nascent transcripts from unproductive degradation by counteracting DIP1

Abstract

Gene expression involves the transcription and splicing of nascent transcripts through the removal of introns. In Drosophila, a double-stranded RNA binding protein Disco-interacting protein 1 (DIP1) targets INE-1 stable intronic sequence RNAs (sisRNAs) for degradation after splicing. How nascent transcripts that also contain INE-1 sequences escape degradation remains unknown. Here we observe that these nascent transcripts can also be bound by DIP1 but the Drosophila homolog of SON (Dsn) protects them from unproductive degradation in ovaries. Dsn localizes to the satellite body where active decay of INE-1 sisRNAs by DIP1 occurs. Dsn is a repressor of DIP1 posttranslational modifications (primarily sumoylation) that are assumed to be required for efficient DIP1 activity. Moreover, the pre-mRNA destabilization caused by Dsn depletion is rescued in DIP1 or Sumo heterozygous mutants, suggesting that Dsn is a negative regulator of DIP1. Our results reveal that under normal circumstances nascent transcripts are susceptible to DIP1-mediated degradation, however intronic sequences are protected by Dsn until intron excision has taken place. During transcription, nascent RNAs are exposed to various RNA degradation machineries in the nucleus. Nascent RNAs undergo a process called splicing that removes noncoding sequences (known as introns) in order to produce protein-coding messenger RNAs. In the vinegar fly Drosophila, introns that contain a transposable sequence known as INE-1 are recognized and degraded by a protein called DIP1. This process usually happens after splicing so that DIP1 does not degrade nascent RNAs. How such a target specificity and temporal control are achieved is not known. Here we found that nascent RNAs are already being recognized by DIP1. However, its activity is inhibited by the SON protein that also binds to nascent RNAs. After splicing, the inhibition of DIP1 by SON is relieved, allowing a spatial and temporal control of DIP1 activity. This regulation is important as it prevents unspecific decay of nascent RNAs that can drastically affect gene expression.