Biology subjects

Gadad, S. S.

Publications and source records attributed to Gadad, S. S..

2 recordsLinked to original sources

bioRxiv2025

Integrated Multi-Omics Analyses of Synaptosomes Revealed Synapse-Centered Novel Targets in Alzheimer's Disease

AO_SCPLOWBSTRACTC_SCPLOWSynapse dysfunction is an early event in Alzheimers disease (AD) caused by various factors such as Amyloid beta, p-tau, inflammation, and aging. However, the exact molecular mechanism of synapse dysfunction in AD is largely unknown. To understand this, we comprehensively analyzed the synaptosome fraction in postmortem brain samples from AD patients and cognitively normal individuals. We conducted high-throughput transcriptomic analyses to identify changes in microRNA (miRNA) and mRNA levels in synaptosomes extracted from the brains of both unaffected individuals and those with Alzheimers disease (AD). Additionally, we performed mass spectrometry analysis of synaptosomal proteins in the same sample group. These analyses revealed significant differences in the levels of miRNAs, mRNAs, and proteins between the groups. To further understand the pathways or molecules involved, we used an integrated omics approach and studied the molecular interactions of deregulated synapse miRNAs, mRNAs, and proteins in the samples from individuals with AD and the control group, which demonstrated the impact of deregulated miRNAs on their target mRNAs and proteins. Furthermore, the DIABLO analysis highlighted complex relationships between mRNAs, miRNAs, and proteins that could be key in understanding the pathophysiology of AD. Our study identified synapse-centered novel candidates that could be critical in restoring synapse dysfunction in AD.

neuroscience↗

bioRxiv2021

Gene structure, differential exon usage, and expression of the testis long intergenic non-protein coding RNA 1016 in humans reveals isoform-specific roles in controlling biological processes

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of biological processes. The constant expansion of newly-identified lncRNA genes requires that each one be comprehensively annotated to understand its molecular functions. Here, we describe a detailed characterization of the gene which encodes long intergenic non-protein coding RNA 01016 (LINC01016, a.k.a., LncRNA1195) with a focus on its structure, exon usage, and expression in human and macaque tissues. In this study, we show that it is exclusively conserved among non-human primates, suggesting its recent evolution and is expressed and processed into 12 distinct RNAs in testis, cervix, and uterus tissues. Further, we integrate de novo annotation of expressed LINC01016 transcripts and isoform-dependent gene expression analyses to show that human LINC01016 is a multi-exon gene, processed through differential exon usage with isoform-specific functions. Furthermore, in gynecological cancers, such as cervical squamous cell carcinoma and uterine corpus endometrial carcinoma, LINC01016 is downregulated; however, its higher expression is predictive of relapse-free survival in these cancers. Collectively, these analyses reveal that, unlike coding RNAs, lncRNA isoforms are differentially regulated and precisely processed in specific tissues to perform distinct biological roles. One sentence summaryThe distinct molecular role of LINC01016 isoforms reveals intricate biology associated with lncRNA transcription and processing.

genomics↗