Sarah is a postdoctoral researcher in the School of Biomedical Engineering, specialising in microRNA biology. Her research areas of interest include understanding how the proteins of the microRNA biogenesis pathway are regulated and determining the tissue-specific transcriptomic landscape of microRNA-associated proteins.
Sarah also is investigating the role plant microRNAs found in honey have in the process of wound healing, and is interested in the potential microRNAs have in cross-species regulation on human processes.
RNA Society Member
- Cross-species microRNA-mediated mechanisms that regulate human gene expression
- Understanding how the microRNA biogenesis and regulatory pathways are controlled
- Human Genetics and Precision Medicine (coming January 2019) – subject coordinator
- DNA sequencing Technologies – Biomedical Engineering undergraduate degree
Hadzhiev, Y, Qureshi, HK, Wheatley, L, Cooper, L, Jasiulewicz, A, Van Nguyen, H, Wragg, JW, Poovathumkadavil, D, Conic, S, Bajan, S, Sik, A, Hutvàgner, G, Tora, L, Gambus, A, Fossey, JS & Müller, F 2019, 'A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation.', Nature Communications, vol. 10, no. 1.View/Download from: Publisher's site
Most metazoan embryos commence development with rapid, transcriptionally silent cell divisions, with genome activation delayed until the mid-blastula transition (MBT). However, a set of genes escapes global repression and gets activated before MBT. Here we describe the formation and the spatio-temporal dynamics of a pair of distinct transcription compartments, which encompasses the earliest gene expression in zebrafish. 4D imaging of pri-miR430 and zinc-finger-gene activities by a novel, native transcription imaging approach reveals transcriptional sharing of nuclear compartments, which are regulated by homologous chromosome organisation. These compartments carry the majority of nascent-RNAs and active Polymerase II, are chromatin-depleted and represent the main sites of detectable transcription before MBT. Transcription occurs during the S-phase of increasingly permissive cleavage cycles. It is proposed, that the transcription compartment is part of the regulatory architecture of embryonic nuclei and offers a transcriptionally competent environment to facilitate early escape from repression before global genome activation.
The Argonaute 2 (Ago2) protein is an essential effector protein in miRNA-mediated
mechanisms that regulate gene expression. Ago2 directly binds to the miRNA, forming
the RISC. RISC function is critical to controlling key biological processes and when
dysregulated can result in disease pathogenesis. Understanding Ago2 protein stability
and turnover will further our understanding in how RISC function is regulated. In human
cells, we discovered a previously unidentified ~55 kDa protein that is a truncated
form of Ago2, that is formed from proteolytic cleavage of the full length Ago2 protein.
Further experiments are needed to determine (i) the detailed mechanism that forms
halfAgo2 (ii) the cellular or environmental triggers or stresses that initiate halfAgo2
production and (iii) if halfAgo2 has a potentially new role in gene regulation.
Connerty, P, Bajan, S, Remenyi, J, Fuller-Pace, FV & Hutvagner, G 2016, 'The miRNA biogenesis factors, p72/DDX17 and KHSRP regulate the protein level of Ago2 in human cells', BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, vol. 1859, no. 10, pp. 1299-1305.View/Download from: Publisher's site
Remenyi, J, Bajan, S, Fuller-Pace, FV, Arthur, JSC & Hutvagner, G 2016, 'The loop structure and the RNA helicase p72/DDX17 influence the processing efficiency of the mice miR-132', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
The majority of human protein-coding genes are predicted to be targets of miRNA-mediated posttranscriptional regulation. The widespread influence of miRNAs is illustrated by their essential roles in all biological processes. Regulated miRNA expression is essential for maintaining cellular differentiation; therefore alterations in miRNA expression patterns are associated with several diseases, including various cancers. High-throughput sequencing technologies revealed low level expressing miRNA isoforms, termed isomiRs. IsomiRs may differ in sequence, length, target preference and expression patterns from their parental miRNA and can arise from differences in miRNA biosynthesis, RNA editing, or SNPs inherent to the miRNA gene. The association between isomiR expression and disease progression is largely unknown. Misregulated miRNA expression is thought to contribute to the formation and/or progression of cancer. However, due to the diversity of targeted transcripts, miRNAs can function as both tumor-suppressor genes and oncogenes as defined by cellular context. Despite this, miRNA profiling studies concluded that the differential expression of particular miRNAs in diseased tissue could aid the diagnosis and treatment of some cancers.
Yagoub, D, Wilkins, MR, Lay, AJ, Kaczorowski, DC, Hatoum, D, Bajan, S, Hutvagner, G, Lai, JH, Wu, W, Martiniello-Wilks, R, Xia, P & McGowan, EM 2014, 'Sphingosine Kinase 1 Isoform-Specific Interactions in Breast Cancer', MOLECULAR ENDOCRINOLOGY, vol. 28, no. 11, pp. 1899-1915.View/Download from: Publisher's site
miRNAs repress the expression of numerous target genes that are involved in a variety of cellular systems, therefore the homeostatic control of miRNA biosynthesis and activity is important for mediating diverse physiological processes such as differentiation, development, immune response, and the cell cycle. Consequently, the misregulation of miRNA function is associated with several pathologies, including cardiovascular diseases, neurological disorders, and cancer. miRNA levels are controlled by the rates of transcription, processing, and turnover. This sequence of steps is subject to complex regulation via mechanisms that can either have a global effect on miRNA generation or specifically modulate the synthesis of a particular miRNA. In this issue of Molecular Cell, Suzuki et al. (2011) provide further evidence that miRNA activity is regulated by mechanisms that target posttranscriptional stages of the maturation of miRNAs by identifying MCPIP1 (monocyte chemoattractant proteins (MCP)-1-induced protein 1), an endo-RNase, that cleaves the loops of multiple miRNAs, leading to their degradation.
Jannot, G, Bajan, SM, Giguère, N, Bouasker, S, Banville, IH, Piquet, S, Hutvagner, GJ & Simard, MJ 2011, 'The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans', EMBO Reports, vol. 12, no. 6, pp. 581-586.View/Download from: Publisher's site
Despite the importance of microRNAs (miRNAs) in gene regulation, it is unclear how the miRNA-Argonaute complex-or miRNA-induced silencing complex (miRISC)-can regulate the translation of their targets in such diverse ways. We demonstrate here a direct in