Viral rna likely forms hairpin structures.  We have a similar problem when we 
tried to sequence GC rich regions.    Try using superscript 3. This Reverse 
transcriptase can work at higher temperatures (not 42C like most other 
RTs)..... we typical used 50-58C for our RT reactions.  A this temps the 
secondary RNA tends to go away allowing the RT reaction to work.

Hope this helps

David Reisman
University of Florida

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Today's Topics:

   1. problems with one step RT-PCR (Dunowska, Magda)


----------------------------------------------------------------------

Message: 1
Date: Fri, 4 Feb 2011 16:55:25 +1300
From: "Dunowska, Magda" <[email protected]>
Subject: problems with one step RT-PCR
To: "[email protected]" <[email protected]>
Cc: "Stickney, Alison" <[email protected]>
Message-ID:
        <92fdfd8b26eb6542b1e1bf017bb998d16990116...@tur-exchmbx.massey.ac.nz>
Content-Type: text/plain; charset="us-ascii"

Hi, my student has run into some problems with the reverese transcriptase PCR 
(RT PCR) assay that I can't quite understand...we are trying to amplify viral 
RNA with published primers designed to amplify 166 bp product. The published 
protocol used FRET probes. We tried this and got no signal. We then decided to 
start from scratch and check the primers with cDNA made from viral RNA (in a 
separate step) with a SYTO dye assay using the AccuMelt (Quanta) PCR mix. We 
got a nice amplification with single melting peaks for all positive samples and 
the right size single band when the reactions were checked on a gel. So, we had 
an amplifiable template and primers that recognised the template. We then added 
the reverse transcriptase to the reaction and included an additional RT step 
before amplification (50 deg C for 10 minutes). This seems to have killed the 
assay - we got no amplification at all. What I couldn't understand is that not 
only we got no signal from tubes with RNA, but we!
 
  also got no amplification in one tube with cDNA (that worked just fine in the 
same reaction without the RT enzyme). We also tried three different commercial 
kits designed for a one-step RT-PCR and got no amplification with any of them. 
So, we can amplify cDNA in a PCR reaction, but when we try to amplify RNA or 
the same cDNA in the RT-PCR reaction we get no amplification at all. I would 
have thought that even if the RT reaction didn't work we should get 
amplification of the cDNA in the RT-PCR assay...Has anybody come across such a 
bizarre thing? It seems like the RT enzyme (we've tried two different enzymes 
from two different manufacturers) interferes with amplification. I used the 
same enzymes/buffers to amplify other viral RNA targets with no problems...Any 
ideas of what might be going on and how to fix it (short of running the assays 
in a two-step format which would be much more expensive and time-consuming)?
Thanks,
Magda






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