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gottspieler
Posted: Wed Mar 03, 2010 9:25 pm    Post subject: Reading an article about TERT..translate please..lol Reply with quote

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ABSTRACT

Constitutive expression of telomerase in human cells prevents the onset of senescence and crisis by maintaining telomere
homeostasis. However, accumulating evidence suggests that the human telomerase reverse transcriptase catalytic subunit
(TERT) contributes to cell physiology independently of its ability to elongate telomeres. Here we show that TERT interacts
with the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a gene that is mutated in the inherited
pleiotropic syndrome cartilage–hair hypoplasia. Human TERT and RMRP form a distinct ribonucleoprotein complex that has
RNA-dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small
interfering RNA in a Dicer (also known as DICER1)-dependent manner. These observations identify a mammalian RdRP
composed of TERT in complex with RMRP.





Questions:

1. what is an RNA-dependent RNA polymerase? I thought all RNA polymerases were RNA dependent?


Human TERT and RMRP form a distinct ribonucleoprotein complex that has
RNA-dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small
interfering RNA in a Dicer (also known as DICER1)-dependent manner.


2. what does the RNA interfere with?

From a single immune complex, we confirmed that either overexpressed
or endogenous TERT interacts with RMRP and TERC, by isolating TAP–TERT (Fig. 1a) or endogenous TERT (Fig. 1b) complexes
in both HeLa and 293T cells under conditions in which we
failed to recover the ribozyme RNase P. We also found that the
abundance of TERT–RMRP and TERT–TERC complexes was similar,
even though TERC was expressed at five-fold higher levels than
RMRP in these cells


3. Please rewrite for the layman...



The TERT–RMRP complex has RdRP activity

4. Does this mean it has a role in gene silencing?
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electricant
Posted: Thu Mar 04, 2010 6:53 pm    Post subject: Reply with quote

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1) An RNA-dependent RNA polymerase is an enzyme which makes an RNA molecule with a sequence that is complementary to an existing RNA sequence (which we call the template). I'm assuming that you understand about complementary base-pairing (ie G binds C and A binds T, or U in the case of RNA).

Messenger RNA is made by DNA-dependent RNA polymerases. DNA is replicated by DNA-dependent DNA polymerases. The HIV virus has an enzyme called reverse transcriptase, which is an RNA-dependent DNA polymerase.

2) Double stranded RNA is uncommon inside cells and is often associated with viral infection. Cells have mechanisms for recognising dsRNA and cuting it up to inactivate it. As well as fighting off viruses, this is also a useful way for cells to silence their own genes under certain circumstances. Small interfering RNAs (siRNAs) bind to complementary sequences in messenger RNA molecules causing them to become degraded, this temporarily silences the gene which codes for this RNA. The siRNAs are interfering with the normal mechanism of gene expression (ie DNA codes for RNA which codes for protein).

3) The group has discovered that when two seperate enzymes (TERT and RMRP) come together they have a totally different enzymatic activity as an RNA-dependent RNA polymerase.

4) Yes! the complex is synthesising complementary RNA strands for normally single stranded RNA. The dsRNA is then broken down by the DICER enzyme to make siRNAs, which are silencing genes by inactivating their RNA products.
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gottspieler
Posted: Fri Mar 05, 2010 9:02 pm    Post subject: Reply with quote

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thanks Razz One day I hope to be as wise as you are...
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