Crystallin gene expression during rat lens development

Abstract

The analysis of the developmental pattern of the aA-, aB-, PSI-, PB2-, ,GB3-, PA3/A1-, and ps-crystallin genes during fetal and postnatal development of the rat shows that the differential regulation of crystallin synthesis relies on differential gene shutdown rather than differential gene activation; that is, all crystallin genes are active during early development but turn off at different stages. The only two exceptions to this rule are the aB-and pscrystallin genes. The aB-crystallin gene transcript becomes first detectable at 18 days of fetal development, while the ps-crystallin gene appears to be active only in the postnatal period.We also determined the absolute numbers of the aA-, aB-, BBl-, pB2-, PB3-, PA3/A1-, ps-, and y-crystallin gene transcripts present in the lens at various times after birth. Comparison of these RNA data with the published protein data shows that the aB-and flB2-crystallin RNAs are relatively overrepresented, suggesting the possibility that these two RNA species are not used as efficiently as other crystallin mRNAs. Examination of the known (hamster) aB-crystallin sequence and elucidation of the (rat) PB2-crystallin sequence yielded no evidence for aberrant codon usage. These two RNAs have one sequence motif in common: they are the only crystallin mRNAs in which the translation initiation codon is preceded by CCACC.The abundant water-soluble proteins of the mammalian lens are encoded by three gene families, the a-, p-and ycrystallin gene families (for review see [l, 21). The a-crystallin gene family has only two members, the aA-and aB-crystallin genes. The protein products of these two genes form the large a-crystallin complex. The p-crystallin gene family is known to have at least six members, of which only four, namely PA3/1-, the PBl-, the BB2-, and the pB3-crystallin sequences, have been cloned. The ,!I-crystallins are found as hetero-oligomers in the lens. The third crystallin gene family, the y-crystallin genes, is evolutionarily related to the fi-crystallin gene family. In the rat the y-crystallin gene family has seven members. Six of these are closely related and encode the monomeric ycrystallins. The seventh codes for the more distantly related monomeric ps-crystallin (for review, see [3]). It has been previously shown that the six y-crystallin genes are all turned on during the early embryonic development of the rat or mouse lens but are differentially shut off during postnatal development [4, 51. As the y-crystallins and the P-crystallins derive from the same ancestral sequence, it is of interest to determine whether the developmental expression of the p-crystallin genes follows the same pattern as that of the y-crystallin genes. If so, these two gene families might have inherited the same mechanism of gene activation. We show that the all members of these two gene Families, except for the ps-crystallin gene, are indeed activated during early embryonic development of the rat lens. We further show that the activation of the aBcrystallin gene lags behind that of the aA-cr...

Biophysical chemistry of the ageing eye lens

“…New cells develop from the epithelial layer via mitosis from which they then differentiate into fibre cells (Mochizuki and Masai 2014). As the new fibre cells develop, they express large amounts of crystallin proteins which are responsible for the refractive index and transparency of the lens (Aarts et al 1989;Zhao et al 2011). Newly differentiated fibre cells migrate towards the lens equator where they undergo denucleation and lose their internal sub-cellular structures (Bassnett 2002;Mochizuki and Masai 2014).…”

“…The lens achieves a high refractive index due to the very high concentration of proteins expressed in the fibre cells (Aarts et al 1989). Lens crystallins show high refractive index increments compared to other proteins, due to large quantities of aromatic and sulphurous residues (Mahendiran et al 2014), and show strong absorbance of UV radiation (Chen et al 2009;Zhao et al 2011).…”

“…Lens fibre cells express the crystallin proteins in high concentrations during their development (Aarts et al 1989). The crystallins form a wide range of oligomeric structures, ranging from monomers in the case of the γ-crystallins (Bloemendal et al 2004), from dimers to octomers in the case of the β-crystallins Bax et al 1990;Lampi et al 1998), and up to 60-mers for the α-crystallins (Horwitz 2003).…”

“…The βA1 and βA3 crystallins are coded by the same gene and differ only in the length of the N-terminus as the βB3 expression is initiated by an earlier start location (Zigler and Sinha 2015). These two proteins are expressed early in the development of the lens and are found primarily in the nucleus, whereas βB2-crystallin is expressed throughout all stages of eye lens growth from a separate gene (Aarts et al 1989). All the acidic β-crystallins are expressed throughout the eye lens in humans with the exception of βA2, which appears in only trace quantities when compared to other mammals (Bloemendal et al 2004).…”

“…βB1-and βB3-crystallins are highly correlated with the β H fraction of the lens crystallins and form into high mass oligomers such as hexamers and octomers (van Montfort et al 2003). Conversely, the β L fraction consists of dimers such as βB2 (Aarts et al 1989). High-mass oligomers of β-crystallin (β H ) (hexamers and octomers) are primarily located in the lens nucleus corresponding to the expression of βB1-and βB3-crystallins and thus are generally found in the oldest lens cells (Aarts et al 1989).…”