Page 30 - IBRO_RNA School_Abstract Book

Evolution of novel regulatory networks from primate spe-

cific lncRNA derived from Alu repeats

Mitali Mukerji

CSIR-Institute of Genomics and Integrative Biology,

Mathura Road, Delhi, India

Annotation of functional elements is one of the major challenges in genomics. This
is because most of the methods primarily assign function through comparative

genomics approaches which cannot account for lineage specific events.
This leaves a bulk of the fraction unannotated and contributes to missing
heritability. Examples of regions of sparse annotations include repeats,
pseudogenes, lncRNAs, circular RNAs to name a few. Primate genomes harbor
a unique family of retrotransposon derived Alu elements that occupy nearly 10%
of the human genome. These have been implicated in a plethora of functions at
different levels of cellular hierarchy and can contribute to novelties even in
conserved regulatory networks. Alus can contribute to different functional
domains of lncRNA but are one of the most difficult to characterize because of
their repetitive nature. Alu repeats in the 3’ UTRs of transcripts are being
increasingly reported in miRNA regulatory networks as they can providing novel
binding sites. Except for isolated instances their role in modulating large-scale

mRNA– miRNA networks is largely understudied. We recently reported a
unique transcript isoform of a CYP20A1 transcript in humans whose 9 kb long
3’UTR harbors 23 Alus, and provides more than 3,000 potential binding sites for
140 different types of miRNAs. Differential expression of this transcript could
sponge an ensemble of miRNAs that can govern specific cellular outcomes in
primary human neurons. These are associated with pathways linked to
coagulation and hemostatic outcomes that are now being implicated in a wide range of
neurodegenerative diseases and neuro-inflammatory conditions.

Reference

Bhattacharya A, Jha V, Singhal K, Fatima M, Singh D, Chaturvedi G, Dholakia D,
Kutum R, Pandey R, Bakken TE, Seth P, Pillai B, Mukerji M Multiple Alu Exoniza-
tion in 3’UTR of a Primate-Specific Isoform of CYP20A1 Creates a Potential
miRNA Sponge. Genome Biol Evol. (2021) Jan 7;13(1):evaa233