GENOMICS 41, 444–452 (1997) ARTICLE NO. GE974704 A Novel Zinc Finger-Containing RNA-Binding Protein Conserved from Fruitflies to Humans F. Rob Jackson,* , ² ,1 Sandro Banfi ,‡ Alessandro Guffanti,‡ and Elena Rossi § ,Ø * Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111; ² Worcester Foundation for Biomedical Research, Shrewsbury, Massachusetts 01545; ‡Telethon Institute of Genetics and Medicine (TIGEM), Via Olgettina, 58, 20100 Milan, Italy; §Servizio di Citogenetica, San Raffaele Biomedical Science Park, Milan, Italy; and Ø Cattedra di Biologia Generale, University of Pavia, Pavia, Italy Received September 23, 1996; accepted February 24, 1997 strategy for cross-species gene identification. It is now The Drosophila lark gene encodes an essential RNA- possible, for example, to search expressed sequence tag binding protein of the RNA recognition motif (RRM) (EST) databases (Boguski et al., 1993) with a given class that is required during embryonic development. query sequence to identify similar genes and/or pro- Genetic analysis demonstrates that it also functions as teins in several different mammalian and invertebrate a molecular element of a circadian clock output path- species quickly. This has permitted large-scale cross- way, mediating the temporal regulation of adult emer- species comparisons of sequences representing differ- gence in the fruitfly. We now report the molecular ent model organisms, and such comparisons, using characterization of a human gene with significant sim- known Drosophila gene sequences, have now identified ilarity to lark. Based on fluorescence in situ hybridiza- many potential human and mouse homologues (Banfi tion and radiation hybrid mapping, the human gene et al., 1996). has been localized to chromosome region 11q13; it is A Drosophila gene known as lark, which is essential closely linked to several identified genes including the for embryonic development, was previously cloned and locus of Bardet–Biedl syndrome type 1. The lark-ho- molecularly characterized (Newby and Jackson, 1993, mologous human gene expresses a single 1.8-kb size 1996). This gene is ubiquitously expressed throughout class of mRNA in most or all tissues including brain. Additional database searches have identified a mouse development and in many different tissues including counterpart that is virtually identical to the human the embryonic nervous system (Newby and Jackson, protein. Similar to lark protein, both mammalian pro- 1993; L. Newby and F. R. Jackson, unpublished data). teins contain two copies of the RRM-type consensus Genetic studies have demonstrated that the lark prod- RNA-binding motif. Unlike most RRM family members, uct also functions as a negative regulatory element of however, the Drosophila and mammalian proteins also the circadian clock output pathway mediating adult contain a retroviral-type (RT) zinc finger that is situ- emergence (Newby and Jackson, 1993, 1996). Subse- ated 43 residues C-terminal to the second RRM ele- quent molecular analysis (Newby and Jackson, 1996) ment. Within a 184-residue segment spanning the RRM has shown that lark protein has striking similarity to elements and the RT zinc finger, the human and mouse members of the RRM class of RNA-binding proteins proteins are 61% similar to the Drosophila lark se- (Query et al., 1989; Burd and Dreyfuss, 1994). Thus, quence. These common sequence features and compar- it has been postulated that the protein executes an isons among a large collection of RRM proteins suggest essential RNA-binding function related to transla- that the human and mouse proteins represent homo- tional control or RNA processing. logues of Drosophila lark.  1997 Academic Press Database searches using lark DNA or protein as a query sequence revealed homology to many other mem- INTRODUCTION bers of the RRM protein family. One of the most sig- nificant matches, however, was with an EST represent- The existence of large and easily accessed nucleic ing a human cDNA clone. We now report the cDNA acid and protein sequence databases has changed the sequence, tissue expression pattern, and chromosomal mapping of the human gene. We also report the com- Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. U89505 and plete sequence of a mouse lark-homologous protein. U89506. This analysis coupled with sequence comparisons 1 To whom correspondence should be addressed at Department among many different RRM proteins suggests that the of Neuroscience, Tufts University School of Medicine, 136 Harrison Drosophila and mammalian genes may be homologues. Avenue, Boston, MA 02111. Telephone: (617) 636-6752. Fax: (617) 636-7413. E-mail: rjackson@opal.tufts.edu. These comparisons also suggest the existence of a novel 444 0888-7543/97 $25.00 Copyright  1997 by Academic Press All rights of reproduction in any form reserved.