Reverse transcription slippage over the mRNA secondary structure of the LIP1 gene

Biotechniques. 2001 Dec;31(6):1286, 1288, 1290, passim. doi: 10.2144/01316st02.

Abstract

The secondary structures in mRNA often cause early termination during the synthesis of cDNA. In an attempt to determine the 5'-untranslated region (UTR) of the gene LIP1 using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE), we found that reverse transcriptases skipped over the LIP1 RNA secondary structures and continued the DNA synthesis through RNA adapter sequences without early termination. A fragment of only three nucleotides upstream of the LIP1 translation initiation codon was obtained from the initial RACE-PCR, which was much shorter than the 57-nucleotide fragment obtained from the cDNA library screening. Analysis of the 5' end sequence indicates the presence of high G+C content and stem-loop secondary structures. Therefore, optimizations of the reaction with high temperature (70 degrees C) and a thermostable reverse transcriptase were performed to synthesize the first-strand cDNA, which was determined to have 73 nucleotides in the 5'-UTR. These results suggest that, under cDNA synthesis conditions at 42 degrees C and 60 degrees C, the reverse transcriptases skipped over the stem-loop structures of LIP1 mRNA and continued the cDNA synthesis until they reached the RNA adapter sequences. Thisfinding draws attention to adopting optimized conditions for cDNA synthesis on G+C-rich RNA templates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Technical Report

MeSH terms

  • 5' Untranslated Regions / genetics
  • Base Sequence
  • DNA, Complementary / genetics
  • Gene Amplification
  • Hot Temperature
  • Humans
  • Lymphoma
  • Molecular Sequence Data
  • Nerve Growth Factors / genetics*
  • Nucleic Acid Conformation
  • Peptide Fragments / genetics*
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction*
  • Transcription, Genetic / genetics
  • Tumor Cells, Cultured

Substances

  • 5' Untranslated Regions
  • DNA, Complementary
  • Nerve Growth Factors
  • Peptide Fragments
  • RNA, Messenger