Regulation of the prereplicative changes in the synthesis and transport of messenger and ribosomal RNA in regenerating livers of normal and hypocalcemic rats

Abstract

Partial hepatectomy induces increases in the synthesis of both messenger (poly(A)⁺) and ribosomal (poly(A)⁻) RNA, which precede the initiation of DNA synthesis. The increase in poly(A)⁺RNA, which commences soon after surgery and reaches a peak 1–3 hours later is particularly striking. Disruption of this early increase in poly(A)⁺RNA synthesis by colchicine (and other microtubule disrupters) or indomethacin results in a failure to initiate DNA synthesis. This suggests that prostaglandins and the microtubules are involved in the mechanism of proliferative activation. Hypocalcemia, which also prevents the initiation of DNA synthesis, has no effect on the prereplicative changes in either messenger or ribosomal RNA synthesis. These results help to define the critical stages of prereplicative development and give some insight into their regulation.