Human Genetics

An RNA of Stature

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Science  14 Oct 2005:
Vol. 310, Issue 5746, pp. 197-199
DOI: 10.1126/science.310.5746.197d

Human growth and stature are regulated in part by the signaling pathways that control cell division and growth. Molecular insights into these pathways have come from the analysis of human mutations that confer clinical abnormalities in stature. One interesting example is cartilage-hair hypoplasia (CHH), a mild form of dwarfism that has been traced to mutations in the RNA subunit of a ribonucleoprotein enzyme (MRP) that cleaves RNA but whose mechanistic role in pathogenesis has been unclear.

Thiel et al. now show that different mutations in MRP RNA cause anauxetic dysplasia, a rare genetic disorder characterized by extreme short stature (adult height <85 cm). After comparing the various mutant RNAs in functional assays, the authors suggest that the clinical differences may arise from differential effects of the mutations on two distinct cellular pathways. Whereas the anauxetic dysplasia mutations appear to severely disrupt processing of ribosomal RNA (presumably leading to inhibition of protein synthesis), the CHH mutations have a modest effect on this pathway but simultaneously disrupt the processing of an mRNA encoding a key cell-cycle regulator. — PAK

Am. J. Hum. Genet., in press.

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