RNA splicing

Trans-spliced leader addition to mRNAs in a cnidarian. Stover, N. A. & Steele, R. E. Proc. Natl Acad. Sci USA 98, 5693–5698 (2001) [PubMed]

Spliced leader (SL) trans-splicing, which replaces the 5′ end of an mRNA with another RNA segment, has only been reported in certain phyla. Because of the many similarities between trans- and cis-splicing, understanding how SL trans-splicing evolved is of biological interest. In March, we highlighted the discovery of SL trans-splicing in a primitive chordate. This paper reports that SL addition also occurs in Hydra, an early diverging metazoan, and indicates that SL trans-splicing might have arisen multiple times.

Gene therapy

Gene therapy restores vision in a canine model of childhood blindness. Acland, G. M. et al. Nature Genet. 28, 92–95 (2001) [PubMed]

Leber congenital amaurosis (LCA), which causes severe retinal degeneration and blindness in children, can result from mutations in RPE65. This paper reports the successful treatment of LCA retinopathy in a naturally occurring dog model of the condition using gene therapy. Subretinal delivery of the wild-type RPE65 gene to RPE65−/− blind dogs restored their sight, as indicated by electrophysiological and behavioural tests. The study provides hope that similar methods will also prove successful in treating retinopathies in humans.

Development

Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development. Kamachi, Y. et al. Genes Dev. 15, 1272–1286 (2001)

PAX6 has a key role in eye and lens development. Kamachi et al. show here that PAX6 and SOX2 initiate lens development by co-operatively binding to lens-specific enhancers; PAX6–SOX2 complex formation in vitro correlates with the activation of a δ-crystallin minimal enhancer in vivo. When ectopicaly expressed, PAX6 and SOX2 cause ectopic lens placode formation, and can thus be considered to function as a genetic switch that initiates lens differentiation.

Human genetics

Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Garcia, C. K. et al. Science April 26 2001 (10.1126/science.1060458) [PubMed]

Familial hypercholesterolaemia (FH) is commonly caused by a defective low-density lipoprotein receptor (LDLR). Now, Garcia et al. have identified the defect that accounts for a rarer form of FH. By positional cloning, they identified the ARH gene (autosomal recessive hypercholesterolaemia), and found mutations in several unrelated FH families. The ARH protein, which includes a conserved phosphotyrosine-binding domain, might bind to the cytoplasmic domain of LDLR itself and function as an 'adaptor' protein.