The Varied Rna Transcript Isoform Landscape During Human Donor Heart Preservation.

Alternative ribonucleic acid (RNA) transcript splicing produces multiple RNA isoforms from the same gene which are associated with many heart diseases. However, little is known about alternative splicing events in donor hearts during cold preservation. We examined the transcriptomic profile of the left ventricle of human donor hearts comparing 0 and 8 hours of cold preservation in histidine-tryptophan-ketoglutarate solution. Differential transcript usage (DTU) analysis was performed to examine for transcript isoform changes. Cold preservation of donor hearts induced a large variety of RNA transcript isoforms. We identified 190 genes showing differential transcript splicing with increasing duration of cold preservation. RNA Isoform switching in 130 genes can be predicted to result in important structural changes in its respective translated proteins. These include altered expression of key protein domains such as intrinsic disorder regions (IDR), and zinc finger domains. Interestingly, cardiac preservation was associated with RNA transcript intron retention or production of a noncoding transcript with no protein product. We identified that ARID5A (figure), a nuclei acid binding protein, had increased expression of a short length variant which results in the loss of IDR regions. ARID5A has important regulatory roles in modulating immune responses at the transcript level. Alternative splicing events occur prominently in human donor hearts during preservation. Genes without overall changes in expression level may have nuanced transcript isoform changes that leads to impaired cardiac preservation quality. Expression of a shortened ARID5A isoform is likely to contribute to immune activation in donor hearts and may affect occurrence of primary graft dysfunction. [ABSTRACT FROM AUTHOR]