Yiannis A Savva

Yiannis A Savva
Brown University · Department of Molecular Biology, Cell Biology and Biochemistry

Ph.D -Molecular biology, Cell biology and Biochemistry

About

22
Publications
3,498
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836
Citations
Additional affiliations
May 2011 - May 2016
Brown University
Position
  • PostDoc Position
Education
May 2011
Brown University
Field of study
  • Molecular Biology, Cellular Biology and Biochemistry
September 2007 - May 2011
Brown University
Field of study
  • Molecular Biology, Cellular Biology and Biochemistry
September 2005 - May 2007
Brown University
Field of study
  • Molecular Biology, Cellular Biology and Biochemistry

Publications

Publications (22)
Article
Full-text available
Heterochromatin formation drives epigenetic mechanisms associated with silenced gene expression. Repressive heterochromatin is established through the RNA interference pathway, triggered by double-stranded RNAs (dsRNAs) that can be modified via RNA editing. However, the biological consequences of such modifications remain enigmatic. Here we show th...
Article
Full-text available
Adenosine to inosine (A-to-I) RNA editing is a post-transcriptional process by which adenosines are selectively converted to inosines in double-stranded RNA (dsRNA) substrates. A highly conserved group of enzymes, the adenosine deaminase acting on RNA (ADAR) family, mediates this reaction. All ADARs share a common domain architecture consisting of...
Article
Full-text available
Auto-regulatory feedback loops are a common molecular strategy used to optimize protein function. In Drosophila, many messenger RNAs involved in neuro-transmission are re-coded at the RNA level by the RNA-editing enzyme, dADAR, leading to the incorporation of amino acids that are not directly encoded by the genome. dADAR also re-codes its own trans...
Article
Full-text available
Background Repetitive elements are now known to have relevant cellular functions, including self-complementary sequences that form double stranded (ds) RNA. There are numerous pathways that determine the fate of endogenous dsRNA, and misregulation of endogenous dsRNA is a driver of autoimmune disease, particularly in the brain. Unfortunately, the a...
Article
Full-text available
Transcription of genetic information from archival DNA into RNA molecule working copies is vital for proper cellular function and is highly accurate. In turn, RNAs serve structural, enzymatic, and regulatory roles, as well as being informational templates for the ribosomal translation of proteins. Following RNA synthesis, maturing of RNA molecules...
Article
Adenosine (A)-to-inosine (I) RNA editing is a fundamental posttranscriptional modifi cation that ensures the deamination of A-to-I in double-stranded (ds) RNA molecules. Intriguingly, the A-toy-I RNA editing system is particularly active in the nervous system of higher eukarotes, altering a plethora of noncoding and coding sequences. Abnormal RNA e...
Article
Full-text available
Background Adenosine-to-inosine RNA editing is a highly conserved process that post-transcriptionally modifies mRNA, generating proteomic diversity, particularly within the nervous system of metazoans. Transcripts encoding proteins involved in neurotransmission predominate as targets of such modifications. Previous reports suggest that RNA editing...
Article
Full-text available
Hundreds of mutations in the SCN1A sodium channel gene confer a wide spectrum of epileptic disorders, requiring efficient model systems to study cellular mechanisms and identify potential therapeutic targets. We have recently demonstrated that Drosophila knock-in flies carrying a GEFS+ causing SCN1A mutation (K1270T) results in a primarily conditio...
Article
Full-text available
A large comparative genomic sequence study has determined the extent of conservation between RNA editing sites within the mammalian evolutionary tree. See related research by Pinto et al., http://genomebiology.com/2014/15/1/R5
Article
Full-text available
The accurate and thorough genome-wide detection of adenosine-to-inosine editing, a biologically indispensable process, has proven challenging. Here, we present a discovery pipeline in adult Drosophila, with 3,581 high-confidence editing sites identified with an estimated accuracy of 87%. The target genes and specific sites highlight global biologic...
Article
Full-text available
Validation and reproducibility of results is a central and pressing issue in genomics. Several recent embarrassing incidents involving the irreproducibility of high-profile studies have illustrated the importance of this issue and the need for rigorous methods for the assessment of reproducibility. Here, we describe an existing statistical model th...
Article
Full-text available
Perhaps no other topic in contemporary genomics has inspired such diverse viewpoints as the 95+% of the genome, previously known as "junk DNA," that does not code for proteins. Here, we present a theory in which dark matter RNA plays a role in the generation of a landscape of spatial micro-domains coupled to the information signaling matrix of the...
Article
Full-text available
Informational recoding by adenosine-to-inosine RNA editing diversifies neuronal proteomes by chemically modifying structured mRNAs. However, techniques for analyzing editing activity on substrates in defined neurons in vivo are lacking. Guided by comparative genomics, here we reverse-engineered a fluorescent reporter sensitive to Drosophila melanog...
Article
Full-text available
Loss of FMR1 gene function results in fragile X syndrome, the most common heritable form of intellectual disability. The protein encoded by this locus (FMRP) is an RNA-binding protein that is thought to primarily act as a translational regulator; however, recent studies have implicated FMRP in other mechanisms of gene regulation. We found that the...
Article
Full-text available
Select proteins involved in electrical and chemical neurotransmission are re-coded at the RNA level via the deamination of particular adenosines to inosine by adenosine deaminases acting on RNA (ADARs). It has been hypothesized that this process, termed RNA editing, acts to “fine-tune” neurophysiological properties in animals and potentially downst...
Article
The depth and complexity of the non-coding transcriptome in nervous system tissues provides a rich substrate for adenosine de-amination acting on RNA (ADAR). Non-coding RNAs (ncRNAs) serve diverse regulatory and computational functions, coupling signal flow from the environment to evolutionarily coded analog and digital information elements within...
Article
Full-text available
The Down syndrome cell adhesion molecule (Dscam) gene has essential roles in neural wiring and pathogen recognition in Drosophila melanogaster. Dscam encodes 38,016 distinct isoforms via extensive alternative splicing. The 95 alternative exons in Dscam are organized into clusters that are spliced in a mutually exclusive manner. The exon 6 cluster c...

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