14.5:
RNA Stability
RNA is a mobile, relatively short-lived molecule that is much less structurally and chemically stable compared to DNA. In RNA, the five-carbon sugar ribose has a hydroxyl group at the second carbon, while deoxyribose has a single hydrogen. The hydrogen of the hydroxyl group is susceptible to being removed in basic solutions. When this occurs, the negatively charged oxygen that remains is capable of breaking the phosphate sugar backbone.
In addition, RNA is usually single stranded, making it less structurally stable than the double helix of DNA. RNA molecules are also much shorter than DNA molecules, so they're more vulnerable to degradation at their ends. External factors can also influence the stability of RNA. For example, specific exonucleases in the cytoplasm called RNases break down RNAs that are not actively being translated. Other proteins, known as RNA-binding proteins effect stability by recognizing and binding to specific RNA nucleotide sequences.
mRNA transcripts with AU-rich elements, usually repeats of AUUUA, in their three-prime untranslated regions, or three-prime UTRs, attract different classes of RNA-binding proteins with opposing roles. Some of these proteins enhance mRNA stability and increase protein translation while bounded to the three-prime UTR, while others destabilize the transcript so that it is degraded more quickly. Thus, the amount of time that an RNA molecule is available for translation is variable and dependent on multiple factors.
14.5:
RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million nucleotides long. RNA has a hydroxyl group on the second carbon of the ribose sugar, increasing the likelihood of breakage of the sugar-phosphate backbone.
The cell can exploit the instability of RNA, regulating both its longevity and availability. More stable mRNAs will be available for translation for a longer period of time than less stable mRNAs transcripts. RNA binding proteins (RBPs) in cells play a key role in the regulation of RNA stability. RBPs can bind to a specific sequence (AUUUA) in the 3’ untranslated region (UTR) of mRNAs. Interestingly, the number of AUUUA repeats appears to recruit RBPs in a specific way: fewer repeats recruit stabilizing RBPs. Several, overlapping repeats result in the binding of destabilizing RBPs. All cells have enzymes called RNases that break down RNAs. Typically, the 5’cap and polyA tail protect eukaryotic mRNA from degradation until the cell no longer needs the transcript.
The emerging research on epitranscriptomics aims to define regulatory mRNA modifications. Recently, scientists have discovered an important role for methylation in mRNA stability. The methylation of adenosine residues (m6A) appears to increase mRNA translation and degradation. m6A also has roles in stress responses, nuclear export, and mRNA maturation. The presence of a modified uracil residue, pseudouridine, also appears to play an important role in RNA regulation.
Suggested Reading
Zhao, Boxuan Simen, Ian A. Roundtree, and Chuan He. “Post-Transcriptional Gene Regulation by MRNA Modifications.” Nature Reviews. Molecular Cell Biology 18, no. 1 (January 2017): 31–42. [Source]
Agris, Paul F. “The Importance of Being Modified: An Unrealized Code to RNA Structure and Function.” RNA 21, no. 4 (April 2015): 552–54. [Source]