000188498 001__ 188498
000188498 005__ 20190316235708.0
000188498 0247_ $$2doi$$a10.1093/nar/gkt695
000188498 022__ $$a1362-4962
000188498 02470 $$2ISI$$a000326044700032
000188498 037__ $$aARTICLE
000188498 245__ $$aA three-state model for the regulation of telomerase by TERRA and hnRNPA1
000188498 269__ $$a2013
000188498 260__ $$aOxford$$bOxford University Press$$c2013
000188498 300__ $$a12
000188498 336__ $$aJournal Articles
000188498 520__ $$aTelomeres, the physical ends of eukaryotic chromosomes, are transcribed into telomeric repeat-containing RNA (TERRA), a large non-coding RNA, which forms an integral part of telomeric heterochromatin. In vitro, naked TERRA molecules are efficient inhibitors of human telomerase, base-pairing via their 5'-UUAGGG-3' repeats with the template sequence of telomerase RNA, in addition to contacting the telomerase reverse transcriptase protein subunit. In vivo, however, TERRA-mediated inhibition of telomerase can be prevented by unknown mechanisms. Also, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has been implicated in telomere length control. In vivo, TERRA is partially associated with hnRNPA1, and hnRNPA1 is also detected at telomeres. We demonstrate that on binding of TERRA, hnRNPA1 can alleviate the TERRA-mediated inhibition of telomerase. However, when in excess over TERRA, hnRNPA1 becomes itself an inhibitor of telomere extension, on binding of the telomeric DNA substrate. Yet, hnRNPA1 has no notable direct effects on the telomerase catalysis. Our in vitro results suggest that TERRA-mediated telomerase inhibition may be prevented by hnRNPA1 in vivo. Telomere extension by telomerase may require balanced levels of TERRA and hnRNPA1 at telomeres. Thus, TERRA and hnRNPA1 can function as a bimolecular regulator to turn telomerase and the telomere on and off.
000188498 700__ $$0243149$$aRedon, Sophie$$g181958
000188498 700__ $$0243157$$aZemp, Ivo$$g198436
000188498 700__ $$0240570$$aLingner, Joachim$$g168670
000188498 773__ $$j41$$k19$$q9117-9128$$tNucleic acids research
000188498 8564_ $$s4544743$$uhttps://infoscience.epfl.ch/record/188498/files/Nucl.%20Acids%20Res.-2013-Redon-9117-28.pdf$$yPublisher's version$$zPublisher's version
000188498 909C0 $$0252147$$pUPLIN$$xU11159
000188498 909CO $$ooai:infoscience.tind.io:188498$$pSV$$particle$$qGLOBAL_SET
000188498 917Z8 $$x168670
000188498 917Z8 $$x182396
000188498 917Z8 $$x148230
000188498 937__ $$aEPFL-ARTICLE-188498
000188498 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000188498 980__ $$aARTICLE