Published online 28 July 2005
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Assigning functions to genes: identification of S-phase expressed genes in Leishmania major based on post-transcriptional control elements
1Department of Parasitology, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School Jerusalem 91120, Israel 2Department of Molecular Genetics and Biotechnology, The Hebrew University-Hadassah Medical School Jerusalem 91120, Israel
*To whom correspondence should be addressed. Tel: 972 2 6758089; Fax: 972 2 6757425; E-mail: Shlomai{at}cc.huji.ac.il
Received May 10, 2005. Revised July 11, 2005. Accepted July 11, 2005.
Assigning functions to genes is one of the major challenges of the post-genomic era. Usually, functions are assigned based on similarity of the coding sequences to sequences of known genes, or by identification of transcriptional cis-regulatory elements that are known to be associated with specific pathways or conditions. In trypanosomatids, where regulation of gene expression takes place mainly at the post-transcriptional level, new approaches for function assignment are needed. Here we demonstrate the identification of novel S-phase expressed genes in Leishmania major, based on a post-transcriptional control element that was recognized in Crithidia fasciculata as involved in the cell cycle-dependent expression of several nuclear and mitochondrial S-phase expressed genes. Hypothesizing that a similar regulatory mechanism is manifested in L.major, we have applied a computational search for similar control elements in the genome of L.major. Our computational scan yielded 132 genes, of which 33% are homologues of known DNA metabolism genes and 63% lack any annotation. Experimental testing of seven of these genes revealed that their mRNAs cycle throughout the cell cycle, reaching a maximum level during S-phase or just prior to it. It is suggested that screening for post-transcriptional control elements associated with a specific function provides an efficient method for assigning functions to trypanosomatid genes.
Present address: Itay Onn, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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