GENETICS: Interfering with Male Fertility

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Science  20 Jul 2001:
Vol. 293, Issue 5529, pp. 395b
DOI: 10.1126/science.293.5529.395b

Repeated sequence elements play an important role in male meiosis and sperm development in the fruit fly Drosophila. One striking example of this is the interaction between the Stellate (Ste) repeats on the X chromosome and the Suppressor of Stellate [Su(Ste)] repeats on the Y chromosome, both of which are expressed in the testis. The Ste locus consists of tandem repeats of an open reading frame (ORF) encoding a subunit of casein kinase 2. In wild-type male flies, expression of these repeats is somehow repressed by the Su(Ste) tandem repeats, which are highly related in sequence to Ste but contain nucleotide substitutions that disrupt the ORFs. Male flies with deletions of the Su(Ste) repeats overexpress Ste and exhibit multiple meiotic abnormalities, including chromosome disorganization and deposition of protein crystals in spermatocytes, which can result in sterility.

Aravin et al. show that Su(Ste) inhibits expression of Ste via an RNA interference mechanism [also known as double-stranded RNA (dsRNA)-mediated gene silencing]. In the wild-type male testis, both strands of Su(Ste) are transcribed, leading to production of short RNAs that can target and eliminate the Ste transcripts [for more on making small RNAs, see Hutvágner et al., Science Express, 12 July 2001, 10.1126/Science.1062961 and Grishok et al., Cell 106, 23 (2001)]. The same gene silencing mechanism also appears to control the level of the Su(Ste) sense-strand RNA, creating a negative feedback loop. These results not only explain the molecular basis of the interaction between Ste and Su(Ste) but also illustrate that RNA interference is a natural mechanism of gene regulation in flies. — PAK

Curr. Biol. 11, 1017 (2001).

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