Person:
Garcia, Susana M. D. A.

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Garcia

First Name

Susana M. D. A.

Name

Garcia, Susana M. D. A.
Author's Publications: search.filters.isAuthorOfPublication.082e23ca-6d35-4747-81c8-93a0fe073ba3

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Small RNA pathway genes identified by patterns of phylogenetic conservation and divergence
    (2013) Tabach, Yuval; Billi, Allison C.; Hayes, Gabriel D.; Newman, Martin; Zuk, Or; Gabel, Harrison; Kamath, Ravi; Yacoby, Keren; Chapman, Brad; Garcia, Susana M. D. A.; Borowsky, Mark L; Kim, John K.; Ruvkun, Gary
    Genetic and biochemical analyses of RNA interference (RNAi) and microRNA (miRNA) pathways have revealed proteins such as Argonaute/PIWI and Dicer that process and present small RNAs to their targets. Well validated small RNA pathway cofactors, such as the Argonaute/PIWI proteins show distinctive patterns of conservation or divergence in particular animal, plant, fungal, and protist species. We compared 86 divergent eukaryotic genome sequences to discern sets of proteins that show similar phylogenetic profiles with known small RNA cofactors. A large set of additional candidate small RNA cofactors have emerged from functional genomic screens for defects in miRNA- or siRNA-mediated repression in C. elegans and D. melanogaster1,2 and from proteomic analyses of proteins co-purifying with validated small RNA pathway proteins3,4. The phylogenetic profiles of many of these candidate small RNA pathway proteins are similar to those of known small RNA cofactor proteins. We used a Bayesian approach to integrate the phylogenetic profile analysis with predictions from diverse transcriptional coregulation and proteome interaction datasets to assign a probability for each protein for a role in a small RNA pathway. Testing high-confidence candidates from this analysis for defects in RNAi silencing, we found that about half of the predicted small RNA cofactors are required for RNAi silencing. Many of the newly identified small RNA pathway proteins are orthologues of proteins implicated in RNA splicing. In support of a deep connection between the mechanism of RNA splicing and small RNA-mediated gene silencing, the presence of the Argonaute proteins and other small RNA components in the many species analysed strongly correlates with the number of introns in that species.
  • Thumbnail Image
    Publication
    Identification of genes in trinucleotide repeat RNA toxicity pathways in C. elegans
    (2014) Garcia, Susana M. D. A.; Tabach, Yuval; Lourenço, Guinevere F.; Armakola, Maria; Ruvkun, Gary
    Myotonic dystrophy disorders are caused by expanded CUG repeats in non-coding regions. To reveal mechanisms of CUG repeat pathogenesis we used C. elegans expressing CUG repeats to identify gene inactivations that modulate CUG repeat toxicity. We identified 15 conserved genes that function as suppressors or enhancers of CUG repeat-induced toxicity and modulate formation of nuclear RNA foci by CUG repeats. These genes regulated CUG repeat-induced toxicity through distinct mechanisms including RNA export and RNA clearance, suggesting that CUG repeat toxicity is mediated by multiple pathways. A subset is shared with other degenerative disorders. The nonsense-mediated mRNA decay (NMD) pathway plays a conserved role regulating CUG repeat RNA transcript levels and toxicity, and NMD recognition of toxic RNAs depends on 3′UTR GC nucleotide content. Our studies suggest a broader surveillance role for NMD where variations in this pathway influence multiple degenerative diseases.