Affiliations: Department of Psychiatry, University of North Carolina
at Chapel Hill, USA. E-mail: {clark_jeffries,diana_perkins}@med.unc.edu | School of Pharmacy, University of North Carolina at
Chapel Hill, USA. E-mail: [email protected] | Renaissance Computing Institute, USA
Note: [] Corresponding author.
Abstract: Homeostatic maintenance of mRNA levels including prompt availability
of mRNAs for translation in response to changing protein demands might be
partly enabled by a system of combinatorial controls involving noncoding RNA
blocking agents. This article proposes a specific version of that control
mechanism, namely, a double-stranded RNA folding from transcription of an
intron of one gene might and leading to an agent that inhibits mRNA of a
counteracting gene. Thus transcription of the first gene would automatically
repress translation of the second. On the basis of a bioinformatics search, we suggest a possible
example, namely, that pro-apoptosis gene PAR4 might inhibit
anti-apoptosis gene XIAP. Part of an intron from PAR4 folds to form
a large, stable hairpin, and reverse complement of the hairpin stem (with
∼280 nucleotides) matches a sub-sequence of an exon in
XIAP. This would be part of an efficient system to drive initiated
apoptosis to its conclusion. Figuratively speaking, it replaces two control
knobs with one. Since repeats, some with many thousands of copies, occur throughout
the genome with complex distributions, care must be taken before asserting that
the presence of any repeat in any gene is significant. Our apoptosis example
involves repeats, so experimental verification is needed and planned. However,
if it is found that the noncoding RNA by-product of one gene folds into a
hairpin that is processed into an agent that inhibits a counteracting gene,
then the same type of control unit might be found extensively among
counteracting families of genes of many types.
Keywords: Counteracting genes, RNA hairpins, noncoding RNA, miRNA, Alu repeat
