Molecular Biology

Local Connections Matter

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Science  18 Sep 2009:
Vol. 325, Issue 5947, pp. 1475
DOI: 10.1126/science.325_1475b

Noncoding (nc)RNAs participate in many cellular processes; they are often associated with the regulation of gene expression, and most specifically with gene silencing—for example, XIST RNA in X-chromosome inactivation and AIR RNA in imprinted gene expression. Telomeres are protein–nucleic acid structures that cap and protect the ends of linear eukaryotic chromosomes. Recently, a noncoding, telomere-repeat–encoded RNA (TERRA) has been found to be transcribed from telomeric DNA.

Deng et al. show that knocking down the levels of TERRA results in a series of telomere defects. TERRA was found to associate with the proteins TRF1 and TRF2, which are components of shelterin, a complex that binds to telomeres. The interaction with TRF2—which localizes TERRA to telomeres—occurs through a domain of the protein that also binds to and localizes the origin recognition complex protein 1 (ORC1) to telomeres. ORC1 is suggested to be part of the telomere maintenance machinery, and TERRA facilitates the interaction between TRF2 and ORC1. Depleting TERRA resulted in both the loss of ORC1 from telomeres and a reduction in heterochromatin at chromosome ends. Furthermore, TERRA is capable of interacting with heterochromatin protein 1, indicating that, as for other ncRNAs, TERRA is involved in promoting heterochromatin formation specifically at telomeres, and that its various interactions contribute to chromosome integrity.

Mol. Cell 35, 403 (2009).

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