Molecular Genetics

Facts

Some RNA base and sugar moieties bear modifications. One modification is a methyl group. Methylation requires S-adenosyl methionine as methyl donor. Targets of methylation include bases, such as some A residues in rRNAs and the terminal G of cap structures, and the 2'OH of riboses, such as those near the caps of nuclear RNA polymerase II transcripts and in internal positions in rRNA.
Some RNAs, in particular tRNAs, contain a variety of modified bases. These base modifications are created by a variety of enzymes, some of which act on tRNA precursors and others of which act on mature tRNAs. Changing the position of the bond between uridine and ribose results in an altered uridine, called pseudouridine (Y). Y is found in rRNA and in tRNA

• The following is known about 2'O-methylation of eucaryotic rRNA:
  • Only specific ribose residues are methylated.
  • The methylation of any one specific ribose depends on the presence of a small nucleolar RNA (snoRNA) which has a short stretch of sequence complementary to the rRNA sequence immediately surrounding the ribose whose methylation the snoRNA is required for.
  • There are many snoRNAs guiding ribose methylation. The rRNA-complementary sequence on these snoRNAs is located between two sequences (box C and box D) conserved among all these snoRNAs.
  • There are two C box--rRNA complement--D box regions in each snoRNA. The two regions are held together by base-paired stem strucutres.
  • Box C+ D snoRNAs are associated with three specific proteins.

Interpretations

• The variety of modifications provides a richness of potential signals not possible with the basic four nucleotides.
• In eucaryotes, the signal for nucleotide residue modification is the sequence immediately surrounding the modifiable residue. The signal is recognized by an RNA molecule capable of base pairing with the signal.
• The enzyme responsible for methylation must be brought in contact with its RNA substrate by its interaction with conserved structures (C and D boxes) in the signal recognizing snoRNA.

Further information

• These modifications (rev) do not alter the coding capacity of those RNAs that are mRNAs. Code-altering changes are known.
• Conversion of U to Y also is mediated by snoRNAs in eukaryotes. These are characterized by a conserved box H and an ACA 3' tail. As with the snoRNAs directing ribose methylation, each of these snoRNAs has two sites for target RNA recognition.
• Modification of tRNAs in eucaryotes and both tRNAs and rRNAs in procaryotes in most cases does not require snoRNAs. Recognition of the modification target is directly by the modifying enzyme.
• RNAs also undergo cleavages and the addition of nucleotides.

This is page 235 of Molecular Genetics by Ulrich Melcher, © 1997, 1998, 1999, 2004