Every RNA has an unique sequence. Since RNAse is an enzyme and substrates react to its active site in a lock-key mechanism, how is RNAse able to degrade any kind of RNA?

  • $\begingroup$ smart question; Note that indeed there are different kinds of RNAses - including those that do not lock on the sequence but rather a different part of the RNA (such as its ends) - and RNAses that lock to the RNA through cofactors such as the RISC complex (which are targeted to certain RNAs by another set of special, sequence-specific RNAs)... $\endgroup$ – tsttst Mar 20 '18 at 4:51
  • $\begingroup$ Welcome to SE Biology. If you read the Help on "How do I ask a good question" you will see that we expect you to “Search, and research” before asking. You do argue your case — although you haven’t asked yourself what the fallacy is in your argument, but you don’t show any evidence of having searched for the answer. Try to do this another time. $\endgroup$ – David Mar 20 '18 at 10:49

Enzymes vary in substrate specificity

This is covered in most textbooks of biochemistry, but you can find explanations on the web, e.g. here. As far as ribonucleases are concerned, there can be high specificity (e.g. recognition of a RNA with a specific base sequence), lower specificity (3′- or 5′-exonucleases — act from these respective ends) or specificity limited to the particular bond to be broken (e.g. pancreatic ribonuclease digests any RNA phosphodiester bond — but not DNA). (There is also specificity of strandedness— between double- and single-stranded RNA.)

What determines this varying specificity?

Evidently, the substrate specificity is determined by the extent of the structure of the substrate that the enzyme has to recognize — i.e. bind to like a ‘lock and key’, refered to in the question. This requires familiarity with the chemistry of the substrate, in this case RNA:

RNA, highlighting the phosphodiester bonds and ribose OH

In the diagram above (modified from Berg et al.) the phosphodiester bond which must be cleaved is highlighted. We can deduce from this diagram that in order to be specific for RNA — but no more — a ribonuclease needs to be able to recognize the ribose 2′OH (i.e. distinguish it from 2′-deoxyribose) as well as recognizing the phosphodiester bond. There is no need to recognize the bases.

The mechanism of action of bovine pancreatic ribonuclease

The mechanism of pancreatic RNase was established in the 1960s, long before any RNase that recognized particular sequences, although it has been refined subsequently. A diagram from the paper by Roberts et al. (1969) is shown below.

Active site of RNase

The diagram does show a ‘pocket’ for one of the bases adjacent to the phosphodiester bond, but this need only be generally hydrophobic, able to accomodate any of the four bases.

To study the interaction of the bases with RNAase one has to obtain crystal structures of RNAase complexed to pseudo-substrates or inhibitors (the true substrate hydrolyses, of course). The literature here is complex, and I am unable to provide a convenient review of the topic. It does appear that the binding of RNA is stabilized by the interaction of particular bases with the protein, but the key point is that any such interactions are not a requisite for the binding of the substrate. As a starting point to the literature I suggest the Protopedia page on RNase A, and a paper by Birdsall and McPherson.

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