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Originally published In Press as doi:10.1074/jbc.M409251200 on January 31, 2005

J. Biol. Chem., Vol. 280, Issue 13, 12397-12404, April 1, 2005
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DTL, the Drosophila Homolog of PIMT/Tgs1 Nuclear Receptor Coactivator-interacting Protein/RNA Methyltransferase, Has an Essential Role in Development*

Orbán Komonyi{ddagger}, Gábor Pápai§, Izzet Enunlu§, Selen Muratoglu§, Tibor Pankotai{ddagger}, Darija Kopitova||, Péter Maróy{ddagger}, Andor Udvardy§, and Imre Boros{ddagger}§**

From the {ddagger}Department of Genetics and Molecular Biology, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary, §Institute of Biochemistry, Biological Research Center, Temesvari körut 62, H-6726 Szeged, Hungary, and || Institute of Gene Biology, Russian Academy of Sciences, Vavilov Street 34/5, Moscow 117 334, Russia

We describe a novel Drosophila gene, dtl (Drosophila Tat-like), which encodes a 60-kDa protein with RNA binding activity and a methyltransferase (MTase) domain. Dtl has an essential role in Drosophila development. The homologs of DTL recently described include PIMT (peroxisome proliferator-activated receptor-interacting protein with a methyltransferase domain), an RNA-binding protein that interacts with and enhances the nuclear receptor coactivator function, and TGS1, the methyltransferase involved in the formation of the 2,2,7-trimethylguanosine (m3G) cap of non-coding small RNAs. DTL is expressed throughout all of the developmental stages of Drosophila. The dtl mRNA has two ORFs (uORF and dORF). The product of dORF is the 60-kDa PIMT/TGS1 homolog protein that is translated from an internal AUG located 538 bp downstream from the 5' end of the message. This product of dtl is responsible for the formation of the m3G cap of small RNAs of Drosophila. Trimethylguanosine synthase activity is essential in Drosophila. The deletion in the dORF or point mutation in the putative MTase active site results in a reduced pool of m3G cap-containing RNAs and lethality in the early pupa stage. The 5' region of the dtl message also has the coding capacity (uORF) for a 178 amino acid protein. For complete rescue of the lethal phenotype of dtl mutants, the presence of the entire dtl transcription unit is required. Transgenes that carry mutations within the uORF restore the MTase activity but result in only partial rescue of the lethal phenotype. Interestingly, two transgenes bearing a mutation in uORF or dORF in trans can result in complete rescue.


Received for publication, August 12, 2004 , and in revised form, January 31, 2005.

* This work was supported by grants from the Hungarian Science Fund (T046414), the Hungarian Ministry of Health (078/2003), and European Community (LSHG-CT-2004-502950). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Hematopoesis Department, University of Maryland, Holland Laboratory, 15601 Crabbs Branch Way, Rockville, MD 20855.

** To whom correspondence should be addressed. Tel.: 36-62-544686; Fax: 36-62-544651; E-mail: borosi{at}bio.u-szeged.hu.


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