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Babaei, S.

Publications and source records attributed to Babaei, S..

3 recordsLinked to original sources

Non-coding circular RNAs repertoire and expression profile during Brassica rapa pollen development

Circular RNAs (circRNAs) are covalently closed long non-coding RNA (lncRNA) molecules generated by the back-splicing of exons from linear precursor mRNAs. Though linear lncRNAs have been shown to play important regulatory roles in diverse biological and developmental processes, little is known about the role of their circular counterparts. In this study, we have performed high-throughput RNA sequencing to delineate the expression profile and potential function of circRNAs during the five stages of pollen development in Brassica rapa. A total of 1180 circRNAs were detected in pollen development, of which 367 showed stage-specific expression patterns. Functional enrichment and metabolic pathway analysis showed that the parent genes of circRNAs were mainly involved in pollen-related molecular and biological processes such as mitotic and meiosis cell division, DNA processes, protein synthesis, protein modification, and polysaccharide biosynthesis. Moreover, by predicting the circRNA-miRNA network from our differentially expressed circRNAs, we found 88 circRNAs with potential miRNA binding sites suggesting their role in post-transcriptional regulation of the genes. Finally, we confirmed the back-splicing sites of 9 randomly selected circRNAS using divergent primers and Sanger sequencing. Our study presents the first systematic analysis of circular RNAs during pollen development and forms the basis of future studies for unlocking complex gene regulatory networks underpinning reproduction in flowering plants.

molecular biology

Genome-wide identification and comparative analysis of Dof gene family in Brassica napus

DOF, DNA binding with one finger proteins are plant-specific transcription factors shown to play roles in diverse plant functions. However, a--little is known about DOF protein repertoire of the allopolyploid crop, Brassica napus. Here, we report genome-wide identification and systematic analysis of the Dof transcription factor family in this important oilseed crop. We identified 117 Brassica napus Dof genes (BnaDofs). So far, this is the largest number of Dof genes reported in a single eudicot species. Based on phylogenetic analysis, BnaDofs were classified into nine groups (A, B1, B2. C1, C2.1, C2.2, C3, D1, D2). Most members belonging to a particular group displayed conserved gene structural organisation and similar protein motifs distribution. Chromosomal localisation analysis highlighted the uneven distribution of BnaDofs across all chromosomes. Evolutionary analysis exemplified that the divergence of Brassica genus from Arabidopsis, the whole genome triplication event, and the hybridisation of B. oleracea and B. rapa to form B. napus, followed by gene loss and rearrangements, led to the expansion and divergence of Dof TF gene family in B. napus. Functional annotation of BnaDof proteins, cis-element analysis of their promoters suggested potential roles in organ development, the transition from vegetative to the reproductive stage, light responsiveness, phytohormone responsiveness as well as abiotic stress responses. Furthermore, the transcriptomic analysis highlighted the preferential tissue-specific expression patters of BnaDofs and their role in response to various abiotic stress. Overall, this study provides a comprehensive understanding of the molecular structure, evolution, and potential functional roles of Dof genes in plant development and abiotic stress response.

plant biology

Genome-wide CRISPR and small-molecule screens uncover targetable dependencies in ATRT

Atypical teratoid rhabdoid tumors (ATRT) are incurable high-grade pediatric brain tumors. Concepts for molecular-driven therapies in ATRTs lag behind, mainly due to the absence of actionable genetic alterations. We performed genome-wide CRISPR/Cas9 knockout screens in six human ATRT cell lines and identified a total of 671 context-specific essential genes. Based on these genetic dependencies, we constructed a library of small-molecule inhibitors that we found to preferentially inhibit growth of ATRT cells. CDK4/6 inhibitors, among the most potent drugs in our library, are capable of inhibiting tumor growth due to mutual exclusive dependency of ATRTs on CDK4 or CDK6. These distinct dependencies drive heterogeneity in response to CDK4/6 inhibitors in ATRTs. Our approach might serve as a blueprint for fostering the identification of functionally-instructed therapeutic strategies in other incurable diseases beyond ATRT, whose genomic profiles also lack actionable alterations so far.

cancer biology