Identification of a family of DNA-binding proteins with homology to RNA splicing factors

Abstract

We describe a unique family of human proteins that are capable of binding to the cAMP regulatory element (CRE) and that are homologous to RNA splicing proteins. A human cDNA was isolated that encodes a protein with a distinctive combination of modular domain structures: 2 leucine-zipper-like domains, a DNA-binding zinc-finger-like domain, an RNA-binding zinc-finger-like domain, and 2 coiled-coil protein-protein interaction domains. It also has a serine-arginine-rich domain, commonly found in proteins involved in RNA splicing. The protein was discovered using the CRE as bait in a yeast 1-hybrid assay. It was then shown to bind specifically to the CRE in vitro using gel shift assays. We have named the protein CRE-associated protein (CREAP). We show that it is widely expressed in human tissues but is highly expressed in several fetal tissues and in several regions of the adult brain. CREAP is closely related to 2 human proteins of unknown function. CREAP shows significant homology with a small nuclear ribonucleoprotein of yeast, Luc7p, involved in 5' splice site recognition. The 3 human CREAP proteins form a unique family with the potential to act as transcription factors that link to RNA processing.

A Functional Screen Reveals an Extensive Layer of Transcriptional and Splicing Control Underlying RAS/MAPK Signaling in Drosophila

“…Namely, some high specificity splicing factors such as the CG10754 (the counterpart of human SF3A2, a U2 small nuclear ribonucleic particle [snRNP] associated factor involved in branch point binding [85]), CG3198 (the ortholog of LUC7L3, a predicted splicing factor [86]), Prp19 (the central component of the PRP19 spliceosomal complex involved in C complex assembly [87]), as well as CG4849 and CG6686 (two predicted tri-snRNP components [88],[89]) all caused a reduction in MAPK protein levels comparable to the EJC factors mago and eIF4AIII . However, no reduction of mapk mRNA was observed by qPCR (Figure 4A; Table S5).…”

LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity

“…LUC7L3 has also been demonstrated as cisplatin resistance-associated protein, cloned from cisplatin resistant cell lines by differential display2021. Independently, LUC7L3 or its closely related human protein has been identified as a protein binding to the cAMP response element (CRE) by the yeast one-hybrid system22. However, the functional roles in the drug resistance or as the CRE-binding protein have not been elucidated.…”

Effects of corticotrophin releasing hormone (CRH) on cell viability and differentiation in the human BeWo choriocarcinoma cell line: a potential syncytialisation inducer distinct from cyclic adenosine monophosphate (cAMP)

“…As a transcription factor, CREB1 binds to a cAMP response element (CRE) sequence in the promoter of target genes, regulating the transcription of those genes [26,27]. CRH has been studied as one of those target genes containing a CRE in the promoter, and the CRE has been shown to be crucial for CRH gene expression [28-30].…”