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3' non-coding region sequences in eukaryotic messenger RNA. ​

Literature Information ​

DOI10.1038/263211a0
PMID822353
JournalNature
Impact Factor48.5
JCR QuartileQ1
Publication Year1976
Times Cited1008
Keywordsnon-coding region, messenger RNA, evolutionary conservation
Literature TypeComparative Study, Journal Article
ISSN0028-0836
Pages211-4
Issue263(5574)
AuthorsN J Proudfoot, G G Brownlee

TL;DR ​

This study identifies a conserved sequence (A-A-U-A-A-A) located approximately 20 residues upstream of the 3'-terminal poly (A) sequence in various purified mRNAs, including alpha- and beta-globulin from rabbits and humans, mouse immunoglobulin light chain, and chicken ovalbumin. The high degree of homology (85%) in the 3' non-coding regions of rabbit and human globulin mRNAs highlights the evolutionary significance of this conservation, suggesting its potential role in mRNA stability or regulation.

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non-coding region · messenger RNA · evolutionary conservation

Abstract ​

The sequence A-A-U-A-A-A is present in six different purified messenger RNA molecules (specifically the alpha-and beta-globulin mRNAs of rabbit and human, the immunoglobulin light chain mRNA of mouse (MOPC 21) and the ovalbumin mRNA of chicken) about 20 residues away from the 3'-terminal poly (A) sequence. In addition, a large selection of the 3' non-coding regions of rabbit and human globulin mRNAs (both the alpha and beta globin mRNAs) are 85% homologous, demonstrating that this region is significantly conserved in evolution.

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Primary Questions Addressed ​

  1. How do variations in the 3' non-coding region affect the stability and translation efficiency of eukaryotic mRNAs?
  2. What evolutionary advantages might arise from the conservation of the 3' non-coding regions in globulin mRNAs across different species?
  3. Are there specific regulatory mechanisms that involve the 3' non-coding region sequences in gene expression modulation?
  4. How do the structural features of the 3' non-coding regions contribute to the binding of regulatory proteins or microRNAs?
  5. In what ways could the study of 3' non-coding regions inform our understanding of diseases related to mRNA dysregulation?

Key Findings ​

Key Insights:

  1. Research Background and Objectives: The study investigates the sequences found in the 3' non-coding regions of eukaryotic messenger RNA (mRNA), focusing specifically on the presence of a conserved sequence motif, A-A-U-A-A-A. The objective is to understand the evolutionary conservation of these sequences and their potential implications for mRNA stability and translation regulation, particularly in well-studied globulin and immunoglobulin mRNAs.

  2. Major Methods and Findings: The researchers analyzed six purified mRNA molecules, including alpha- and beta-globulin mRNAs from rabbits and humans, immunoglobulin light chain mRNA from mice (MOPC 21), and ovalbumin mRNA from chickens. By sequencing these mRNAs, they identified the A-A-U-A-A-A motif located approximately 20 nucleotides upstream of the 3'-terminal poly(A) tail. Furthermore, through comparative analysis, they found that the 3' non-coding regions of rabbit and human globulin mRNAs exhibited an 85% homology, indicating significant evolutionary conservation.

  3. Core Conclusions: The presence of the A-A-U-A-A-A sequence motif in multiple eukaryotic mRNAs suggests that this sequence may play a critical role in mRNA function. The high degree of homology in the 3' non-coding regions of globulin mRNAs from different species implies that these sequences are evolutionarily conserved, which may be indicative of their importance in processes such as mRNA stability, localization, or translation efficiency.

  4. Research Significance and Impact: This research enhances our understanding of the regulatory elements present in the 3' non-coding regions of mRNAs and their evolutionary significance. The conservation of specific sequences across different species suggests that they may be fundamental to the molecular mechanisms governing gene expression in eukaryotes. These insights could pave the way for further studies into mRNA stability and translation in various biological contexts, as well as potential applications in biotechnology and medicine, such as the development of mRNA-based therapeutics. Understanding these sequences could also provide a foundation for exploring the roles they play in diseases where mRNA regulation is disrupted.

Literatures Citing This Work ​

  1. Rous sarcoma virus genome is terminally redundant: the 3' sequence. - D E Schwartz;P C Zamecnik;H L Weith - Proceedings of the National Academy of Sciences of the United States of America (1977)
  2. Analysis of the 3'-terminal nucleotide sequence of vesicular stomatitis virus N protein mRNA. - D J McGeoch;N T Turnbull - Nucleic acids research (1978)
  3. Sequence homology adjacent to the 3' terminal poly(A) of cowpea mosaic virus RNAs. - J W Davies;J Stanley;A Van Kammen - Nucleic acids research (1979)
  4. Nucleotide sequences from the 3'-ends of vesicular stomatitis virus mRNA's as determined from cloned DNA. - J K Rose;L Iverson - Journal of virology (1979)
  5. Polyoma virus. The early region and its T-antigens. - E Soeda;J R Arrand;B E Griffin - Nucleic acids research (1979)
  6. The bicistronic nature of lens alpha-crystallin 14S mRNA. - J H Chen;A Spector - Proceedings of the National Academy of Sciences of the United States of America (1977)
  7. Host factor for coliphage Q beta RNA replication: presence in procaryotes and association with the 30S ribosomal subunit in Escherichia coli. - M S DuBow;T Ryan;R A Young;T Blumenthal - Molecular & general genetics : MGG (1977)
  8. Molecular cloning and nucleotide sequence of the human growth hormone structural gene. - W G Roskam;F Rougeon - Nucleic acids research (1979)
  9. The 3' noncoding region of beta-globin mRNA is not essential for in vitro translation. - M N Kronenberg;B E Roberts;A Efstratiadis - Nucleic acids research (1979)
  10. 5' and 3' terminal nucleotide sequences of the RNA genome segments of influenza virus. - J S Robertson - Nucleic acids research (1979)

... (998 more literatures)

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