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Searles, Lillie L.

Professor Emeritus
508 Fordham Hall
(919) 966-4989 (office)

In eukaryotes, regulated RNA degradation is important for numerous processes, such as the modulation of gene expression, quality control during mRNA synthesis, and defense against RNA viruses. Since RNA degradation enzymes are ubiquitous, this process must be carefully controlled so that only the appropriate targets are recognized and degraded. Much remains to be learned about how this control is achieved, especially in multi-cellular organisms.

We have obtained evidence that Suppressor of sable protein [Su(s)] of Drosophila participates in nuclear RNA quality control. Su(s) is an RNA binding protein that associates with genes as they are being transcribed and inhibits the accumulation of specific aberrant transcripts—mutant alleles with transposon insertions that affect splicing; heat-shock inducible RNAs produced from tandemly-repeated transposons in the vicinity of a heat shock locus; and cryptic transcripts produced from a wild-type gene at an inappropriate time, when neighboring genes are being expressed. Other results indicate that Su(s) promotes degradation of these RNAs by the nuclear exosome.

Currently, we are further investigating the mechanism involved. There are at least two different RNA quality control systems in the nucleus, and one of our goals is to determine if Su(s) functions in one of the known pathways or some other process. In addition, we are working to define the RNA sequences that are bound by Su(s) and to determine if these sites are enriched in a particular region of RNAs, e.g. coding versus noncoding sequences. Our approach to these questions is multifaceted in that we use genetic, biochemical, molecular, cell biological and genomic methods.

The results of this research will provide new insights into nuclear RNA degradation mechanisms in multi-cellular organisms and help to clarify how defective RNAs are identified by the nuclear quality control machinery. The presence of multiple RNA quality control systems and the high degree of similarity in the general components of these systems indicate that this is a vitally important process for most, if not all, eukaryotic organisms.