THE HUMAN RIL GENE - MAPPING TO HUMAN-CHROMOSOME 5Q31.1, GENOMIC ORGANIZATION AND ALTERNATIVE TRANSCRIPTS

The ril gene encoding a LIM domain protein of an unknown function was previously identified by differential expression cloning as a candidat e tumor suppressor gene in rat fibroblasts (Kiess, M., Scharm, B., Agu zzi, A., Hajnal, A., Klemenz, R., Schwarte-Waldhoff, I., Schafer, R., 1995. Expression of ril, a novel LIM domain gene, is down-regulated in HRAS-transformed cells and restored in phenotypic revertants. Oncogen e 10, 61-68). Searching for novel genes on human chromosome 5q31.1 by the cDNA selection technique, we isolated a cDNA clone identical with the cDNA of the human RIL gene (GenBank Accession No. X93510). The hum an 5q31.1 region is of interest because it contains the cytokine gene cluster and is frequently deleted in the malignant cells of patients w ith myelodysplasia and myeloid leukemia. Using Southern blot analysis and restriction mapping of genomic YAC (yeast artificial chromosome) a nd cosmid clones, we located the human RIL gene 240-260 kb telomeric t o the IRF1 gene and characterized its genomic structure. PCR analysis indicated the presence of two alternative RTL transcripts in human fet al brain mRNA. The major transcript is identical with the RIL cDNA pre viously deposited in GenBank and contains seven exons distributed over 14.5 kb of genomic DNA with the two last 3'-exons coding a LIM domain . The minor transcript lacks the sixth exon compared with the major tr anscript, which leads to the loss of the LIM domain. We also identifie d two putative transcription start points (tsp) and sequenced the 5'-f lanking region of RIL to reveal potential binding sites for transcript ional factors. (C) 1998 Elsevier Science B.V.