IDENTIFICATION OF THE START SITES FOR THE 1.9-KB AND 1.4-KB RAT TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSCRIPTS AND THEIR EFFECT ON TRANSLATIONAL EFFICIENCY

Three distinct transforming growth factor-beta 1 (TGF-beta 1) transcri pts of 2.5, 1.9 and 1.4 kb have been described, but the start sites an d functional significance of the shorter transcripts are unknown. Here , we have cloned and sequenced a rat genomic fragment encoding similar to 1250 bases upstream of the start of the TGF-beta 1 open reading fr ame. Using a combination of ribonuclease protection and 5' RACE-PCR an alysis, we have mapped the start sites for the two shorter TGF-beta 1 transcripts in NRP152 cells, a rat prostatic epithelial cell line that expresses all three transcripts at high levels. The 1.4-kb mRNA start s 25 bases upstream of the initiator AUG, whereas the 1.9-kb mRNA has two start sites 366 and 401 bases upstream of the AUG. Polysome analys is of the NRP152 cells indicates that the 1.9-kb transcript is very ef ficiently translated, whereas the 2.5- and 1.4-kb transcripts appear t o be poorly translated. Differential regulation of TGF-beta 1 transcri pt size may therefore represent an important mechanism for regulating TGF-beta 1 protein levels. (C) 1998 Elsevier Science B.V. All rights r eserved.