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Abstract: TH-PO0995

Uncovering the Role of Noncoding RNA in Kidney Transplant Pathology

Session Information

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Josephson, Michelle A., The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Coe, Jason Andrew, MesoRNA, Chicago, Illinois, United States
  • Coe, Fredric L., The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Chang, Anthony, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Kyeso, Yousuf, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Katanski, Christopher D., MesoRNA, Chicago, Illinois, United States
  • Dubin, Reece J., MesoRNA, Chicago, Illinois, United States
  • Tran, Hoang Anh V., The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Bayat Tork, Mohammad Amin, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Pan, Tao, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
Background

Extensive evidence points to the role of tRNA and snoRNA dysfunction in disease processes.tRNAs read the genetic code and provide amino acids in translation.SnoRNAs guide rRNA modifications and facilitate protein secretion.Advances in our understanding are undermined by technical obstacles that limit their sequencing.We have developed multiplex small RNA sequencing (MSR-seq, PMID 35513407) technology that enables the assessment of tRNA/snoRNA expression, tRNA modification, fragmentation, and charging.

Methods

Using MSR-seq, we explored tRNA and snoRNA differences in 2 distinct states of kidney transplant dysfunction: acute tubular necrosis (ATN) and T cell mediated rejection (TCMR).We performed a retrospective analysis of formalin fixated paraffin embedded (FFPE) biopsy samples from 11 patients diagnosed with ATN and 9 with TCMR.

Results

We found that TCMR upregulates the expression of multiple snoRNAs (Fig.1) and downregulates the expression of specific mitochondrial tRNAs compared with ATN. Furthermore, TCMR showed global decreases in certain tRNA modification levels compared with ATN, such as the microbiome dependent queuosine (Q) modification.

Conclusion

Overexpression of snoRNAs, including those identified in our study such as SNOR6, has been associated with drug resistance. In addition, reduction in tRNA modification has been linked to the innate immune response.Our findings on their differential abundance and modification levels highly suggest that these abundant, mid-sized non-coding RNAs participate in transplant processes.Further studies of these non-coding RNAs in transplant will further our understanding of their role and may provide useful biomarkers and potential therapeutic targets.

Fig 1.