Messenger RNA for cataractous lens proteins are also present on normal lens polyribosomes

We have previously described an experimental model in vivo where cataract is induced by injection of the antimitotic bleomycin in the newborn rat. The first opacity of the lens appears 12--15 days after the injection of the drug concomitantly with a group of precise biochemical modifications among the soluble crystallins. These modifications are mainly the accumulation of two additional low-molecular-weight beta crystallin subunits (beta L subunits) and of several smaller alpha-crystallin polypeptides. Messenger RNA isolated from normal and cataractous lenses was assayed for translation in a cell-free wheat germ extract. Analysis of the translation products by one-dimensional and two-dimensional gel electrophoresis indicated that the messenger RNAs coding for the two beta L subunits are also present on normal lens polyribosomes. Purification and subsequent analysis by peptide mapping of the cataractous Beta L subunits suggest that they are precursor polypeptides of the normal low-molecular-weight beta-crystallins, which are no longer processed after translation and therefore accumulate in the pathological lens cell. On the other hand, in the translation of the cataractous mRNA in vitro, only the normal alpha chains are detected. These cataractous alpha-crystallins are therefore post-translational degradation products of the normal alpha polypeptides. This phenomenon seems similar to the one observed in the senescent lens. The possible involvement of these modifications in the etiology of this experimental cataract is discussed further.