Molecular Biology

A Tail of Two Cids

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Science  20 Dec 2002:
Vol. 298, Issue 5602, pp. 2287
DOI: 10.1126/science.298.5602.2287a

The discovery of how small RNA molecules (about 22 to 28 nucleotides in length) regulate gene expression (see Breakthrough of the Year, p. 2296) portends a renaissance of interest in this class of biopolymers. Genetic information encoded in DNA is first extracted by transcription into pre-messenger RNA (pre-mRNA), then exons are spliced together to produce a mature mRNA, which is exported from the nucleus into the cytoplasm. All of these processes are tightly regulated, yet recent results indicate that the cytoplasmic mRNA may be subject to another round of regulation that determines when that genetic information is finally converted into usable proteins.

Juge et al. show that Drosophila contain a single poly(A) polymerase, the enzyme responsible for polyadenylating mRNAs and rendering them competent for export and translation, that is present and active in both the nucleus and cytoplasm. A cytoplasmic surplus of this enzyme results in excessively long poly(A) tails and embryonic lethality, hinting at regulatory control of adenylation during development. Additional evidence for the connection between poly(A) tails and germline and embryonic development comes from Wang et al., who find that the Caenorhabditis protein GLD-2 is the catalytic portion of a cytoplasmic poly(A) polymerase. They propose that its activity may be directed by interaction with RNA-binding recruiter proteins.

Fission yeast refrain from dividing until DNA replication is complete; hydroxyurea, a cancer therapeutic which inhibits synthesis of deoxyribonucleotides, activates the replication checkpoint. Saitoh et al. and Read et al. have identified cytoplasmic poly(A) polymerases (Cid1 and Cid13) as components of the cellular response that overcomes arrest at this checkpoint, suggesting a general involvement of these enzymes in eukaryotic processes. — GJC

EMBO J.21, 6603 (2002); Nature419, 312 (2002); Cell109, 563 (2002); Proc. Natl. Acad. Sci. U.S.A.99, 12079 (2002).

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