Poster abstracts
Poster number 118 submitted by Joe Seimetz
Developmental reprogramming of the transcriptome is an essential component of liver regeneration
Joseph Seimetz (UIUC Department of Biochemistry), Amruta Bhate (UIUC Department of Biochemistry), Edrees H Rashan (UIUC Department of Biochemistry), Waqar Arif (UIUC Department of Biochemistry), Sayeepriyadarshini Anakk (UIUC Department of Molecular and Integrative Physiology), Auinash Kalsotra (UIUC Department of Biochemistry)
Abstract:
Tissue regeneration is a vital mechanism in mature organisms to recover from injury. The mammalian liver—a major metabolic organ in the body—has the unique capacity to undergo robust regeneration in response to damage. Interestingly, this response can be proliferative, hypertrophic, or a combination of both. However, the molecular mechanisms that drive this terminally differentiated tissue into a proliferative and hypertrophic state remain elusive. To determine the underlying mechanisms, we performed a high resolution RNA-seq on toxin-induced, regenerating mouse livers. We identified dramatic changes at both the transcriptional and post-transcriptional levels that cluster to specific cellular processes. Surprisingly, we determined a reciprocal set of mRNA abundance and splice isoform transitions that are normally active during postnatal liver development. We further verified several hundred of these isoform transitions by PCR within individual genes to verify their directionality, temporal dynamics, and cell-type specificity. A computational framework to correlate the regeneration-associated transitions and various cis elements identified a number of RNA-binding proteins that are significantly associated with these splicing alternations. Within this data we identified a subset of developmentally regulated RNA-binding proteins and splicing factors that are markedly induced in the regenerating livers. This suggests that after sustaining damage, these factors are instrumental in activating an embryonic-associated splicing program to support the regenerative process. In summary, our results demonstrate that after sustaining damage, an early postnatal, splicing regulatory network is redeployed in the adult mammalian liver to facilitate regeneration.
Keywords: alternative splicing, development, RNA-binding proteins