Education & Certifications
MS, University of Pennsylvania, Chemistry (2011)
Modulation of MicroRNA Expression and Function by ADARs
ADENOSINE DEAMINASES ACTING ON RNA (ADARS) AND A-TO-I EDITING
2012; 353: 91-109
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by preventing the translation of specific messenger RNAs. Adenosine deaminases acting on RNAs (ADARs) catalyze adenosine-to-inosine (A-to-I) RNA editing, the conversion of adenosines into inosines, in double-stranded RNAs. Because inosine preferentially base pairs with cytidine, this conversion is equivalent to an adenosine to guanosine change. Over the past seven years, an increasing number of edited adenosines have been identified in miRNAs. Editing of miRNAs affects their biogenesis, causes their degradation or alters the set of messenger RNAs that they regulate. Recently, ADARs have been shown to also affect the miRNA phenomenon by sequestering miRNAs or by editing the messenger RNAs they regulate. This article reviews the recent attempts to identify miRNA editing sites and elucidate the effects of ADARs on miRNA expression and function.
View details for DOI 10.1007/82_2011_151
View details for Web of Science ID 000303685600004
View details for PubMedID 21761289
Elucidating the inosinome: global approaches to adenosine-to-inosine RNA editing
NATURE REVIEWS GENETICS
2011; 12 (2): 81-85
Catalysed by members of the adenosine deaminase acting on RNA (ADAR) family of enzymes, adenosine-to-inosine (A-to-I) editing converts adenosines in RNA molecules to inosines, which are functionally equivalent to guanosines. Recently, global approaches to studying this widely conserved phenomenon have emerged. The use of bioinformatics, high-throughput sequencing and other approaches has increased the number of known editing sites by several orders of magnitude, and we now have a greater understanding of the control and the biological significance of editing. This Progress article reviews some of these recent global studies and their results.
View details for DOI 10.1038/nrg2915
View details for Web of Science ID 000286319600009
View details for PubMedID 21173775
View details for PubMedCentralID PMC3075016
Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency.
journal of biological chemistry
2010; 285 (43): 33358-33370
Certain primary transcripts of miRNA (pri-microRNAs) undergo RNA editing that converts adenosine to inosine. The Epstein-Barr virus (EBV) genome encodes multiple microRNA genes of its own. Here we report that primary transcripts of ebv-miR-BART6 (pri-miR-BART6) are edited in latently EBV-infected cells. Editing of wild-type pri-miR-BART6 RNAs dramatically reduced loading of miR-BART6-5p RNAs onto the microRNA-induced silencing complex. Editing of a mutation-containing pri-miR-BART6 found in Daudi Burkitt lymphoma and nasopharyngeal carcinoma C666-1 cell lines suppressed processing of miR-BART6 RNAs. Most importantly, miR-BART6-5p RNAs silence Dicer through multiple target sites located in the 3'-UTR of Dicer mRNA. The significance of miR-BART6 was further investigated in cells in various stages of latency. We found that miR-BART6-5p RNAs suppress the EBNA2 viral oncogene required for transition from immunologically less responsive type I and type II latency to the more immunoreactive type III latency as well as Zta and Rta viral proteins essential for lytic replication, revealing the regulatory function of miR-BART6 in EBV infection and latency. Mutation and A-to-I editing appear to be adaptive mechanisms that antagonize miR-BART6 activities.
View details for DOI 10.1074/jbc.M110.138362
View details for PubMedID 20716523
View details for PubMedCentralID PMC2963350
Substitutional A-to-I RNA editing
WILEY INTERDISCIPLINARY REVIEWS-RNA
2010; 1 (1): 90-101
Adenosine-to-inosine (A-to-I) editing catalyzed by adenosine deaminases acting on RNA (ADARs) entails the chemical conversion of adenosine residues to inosine residues within double-stranded RNA (dsRNA) substrates. Inosine base pairs as guanosine and A-to-I editing can therefore alter the structure and base pairing properties of the RNA molecule. This has a biological significance in controlling the amount of functional RNA molecules in the cell, in expanding the functionality of a limited set of transcripts, and in defending the cell against certain RNA viruses. A-to-I editing is not limited to any specific type of RNA substrate. Instead, it can affect any RNA molecule able to attain the required double-stranded structure. This includes microRNAs, small interfering RNAs, viral RNAs, and messenger RNAs with potential for recoding events and splice site modifications.
View details for DOI 10.1002/wrna.10
View details for Web of Science ID 000208267100008
View details for PubMedID 21072321
View details for PubMedCentralID PMC2976053