A
team from the "Laboratoire de Biologie Moléculaire Eucaryote"
(LBME, Eukaryotic Molecular Biology Laboratory, Toulouse) has identified
a class of small nucleolar RNAs (snoRNAs) expressed exclusively in
the mammalian brain. They suggest this class of snoRNAs may be involved
in controlling brain-specific genes by selectively modifying the structure
of certain messenger RNAs. They have demonstrated that a subset of
these snoRNAs is absent in persons who suffer from one of the most
common congenital disorders, the Prader-Willi syndrome.
Most
genes are transcribed into messenger RNAs which are then translated
via ribosomes into proteins. Some RNAs, however, are non-coding. Most
non-coding RNAs are involved in the conversion of gene transcripts
into functional RNA by eliminating superfluous portions. A major subset
of non-coding RNAs correspond to snoRNAs, small RNAs which accumulate
in the nucleolus. Most snoRNAs target the chemical modification of
some ribosomal RNA nucleotides. The team identified four new snoRNAs
in this nucleotide-modifying class that do not target ribosomal RNA
and are expressed only in the brain; the genes for 3 of these are
located in a chromosomal locus submitted to parental genomic imprinting.
Prader-Willi syndrome is associated with an altered expression of
paternally inherited genes in that locus. The team has shown that
these snoRNAs cannot be detected in people with the syndrome and thus
constitute possible candidates for the cause of Prader-Willi syndrome.
One
of the novel snoRNA may direct ribose methylation of a particular
mRNA coding for a serotonin receptor. Ribose methylation is normally
irrelevant to decoding mRNA information, but this modification occurs
at a site which undergoes editing, altering mRNA decoding, thus changing
the peptide sequence of the serotonin receptor. Thus the snoRNA may
indirectly alter the editing reaction. The importance in gene expression
of posttranscriptional modification of mRNA nucleotides may therefore
have to be reexamined.
