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You searched for subject:(miRNA biogenesis ). Showing records 1 – 3 of 3 total matches.

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Penn State University

1. Song, Liang. THE BIOGENESIS OF MIRNA AND THE BIOLOGICAL FUNCTION OF THE ATMIR171A GENE IN ARABIDOPSIS THALIANA.

Degree: PhD, Plant Physiology, 2008, Penn State University

MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs that are involved in post-transcriptional gene silencing. In this study, an Arabidopsis miRNA gene, AtMIR171a, was characterized and used as a model to study the biogenesis and function of plant miRNAs. AtMIR171a is a strongly conserved miRNA that is expressed at high levels in Arabidopsis. The transcription unit of the AtMIR171a gene is quite complex. It has at least three transcription start sites, Pri-I, -II and -III. It also contains alternative splice sites and alternative polyadenylation sites. Most transcripts of the AtMIR171a locus initiate at the transcription start site Pri-I located 74 bp upstream of the putative AtMIR171a-containing stem-loop. The complexity of the gene structure may reflect the low selection pressure exerted outside the stem-loop structure. Mutations in three genes have been identified to affect miRNA accumulation in Arabidopsis. These genes are Dicer-like1 (DCL1), Hua Enhancer1 (HEN1) and Hyponastic Leaves1 (HYL1). DCL1 encodes an RNase III enzyme that cleaves miRNA precursors to generate mature miRNAs. HEN1 codes for a methyltransferase that prevents uridylation and degradation of small RNAs by methylating the ribose of the 3’-most nucleotides in the miRNA:miRNA* or siRNA:siRNA* duplex. HYL1 encodes a double-stranded RNA binding protein (dsRBP) which has two double-stranded RNA binding motifs (DSRM) in its N-terminal region. Three lines of evidence suggest that HYL1 and DCL1 act in the same step in miRNA biogenesis. First, the loss-of-function homozygotes of dcl1 and hyl1 exhibit similar development defects. Second, the accumulation of mature miRNA is reduced in both dcl1 and hyl1 mutant plants. Third, a previous study showed that a dsRBP R2D2 facilitates an RNase III protein DCR-2 in loading siRNA into the RNA-induced silencing complex (RISC) in Drosophila. This suggests that an RNase III enzyme interacts with a specific dsRBP in gene silencing. To test whether HYL1 acts with DCL1 in miRNA biogenesis, the amounts of AtMIR171a precursors were measured by northern blotting and RT-PCR. The results showed that unlike hen1 homozygotes, which do not accumulate pri-AtMIR171a, both hyl1 and dcl1 mutants have much greater amounts of pri-AtMIR171a than wildtype plants. Therefore the paucity of mature AtMIR171a in hyl1 and dcl1 mutant plants is not attributable to either reduced miRNA stability or decreased transcription from the AtMIR171a gene, but is caused by a defect in the processing of pri-miRNA. In addition to the genetic evidence, the co-localization of HYL1 and DCL1 in the nucleoplasm and in perinucleolar bodies further supports the notion that these two proteins function together in miRNA biogenesis. The HYL1-DCL1-containing bodies are distinguishable from Cajal bodies, which contains the DCL3-dependent siRNA silencing machinery, because neither Arabidopsis Cajal body marker, AtCoilin or U2B”, co-localizes with HYL1. When HYL1 and SE, another protein involved in miRNA biogenesis, were co-expressed in Arabidopsis mesophyll…

Subjects/Keywords: DCL1; Arabidopsis; SCL; miR167a; miR171a; HYL1; miRNA biogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Song, L. (2008). THE BIOGENESIS OF MIRNA AND THE BIOLOGICAL FUNCTION OF THE ATMIR171A GENE IN ARABIDOPSIS THALIANA. (Doctoral Dissertation). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/9471

Chicago Manual of Style (16th Edition):

Song, Liang. “THE BIOGENESIS OF MIRNA AND THE BIOLOGICAL FUNCTION OF THE ATMIR171A GENE IN ARABIDOPSIS THALIANA.” 2008. Doctoral Dissertation, Penn State University. Accessed January 25, 2020. https://etda.libraries.psu.edu/catalog/9471.

MLA Handbook (7th Edition):

Song, Liang. “THE BIOGENESIS OF MIRNA AND THE BIOLOGICAL FUNCTION OF THE ATMIR171A GENE IN ARABIDOPSIS THALIANA.” 2008. Web. 25 Jan 2020.

Vancouver:

Song L. THE BIOGENESIS OF MIRNA AND THE BIOLOGICAL FUNCTION OF THE ATMIR171A GENE IN ARABIDOPSIS THALIANA. [Internet] [Doctoral dissertation]. Penn State University; 2008. [cited 2020 Jan 25]. Available from: https://etda.libraries.psu.edu/catalog/9471.

Council of Science Editors:

Song L. THE BIOGENESIS OF MIRNA AND THE BIOLOGICAL FUNCTION OF THE ATMIR171A GENE IN ARABIDOPSIS THALIANA. [Doctoral Dissertation]. Penn State University; 2008. Available from: https://etda.libraries.psu.edu/catalog/9471


University of Technology, Sydney

2. Connerty, Patrick Peter. Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins.

Degree: 2016, University of Technology, Sydney

microRNAs (miRNAs) are small non-coding RNAs which post-transcriptionally regulate gene expression. As miRNAs control many important biological processes it is important that their own production is highly controlled too. A range of auxiliary proteins involved in regulating miRNA biogenesis have been documented extensively, highlighting the complexity of the miRNA pathway. This study identifies novel roles of RNA binding proteins which are both canonical and auxiliary to the miRNA biogenesis pathway. Here, we demonstrate that inhibition of p72 and KHSRP decreases Ago2 protein stability through disturbing miRNA biogenesis and therefore miRNA abundance. Furthermore, we have demonstrated that Ago2 is subject to multiple types of regulation as transient knockdown of Dicer stabilises Ago2 protein despite a decrease in miRNA abundance via an unknown mechanism. Additionally, we have established that miRNA biogenesis is subject to a possible negative feedback mechanisms in which impairment of Dicer function both promotes and inhibits pri-miRNA production in a pri-miRNA and cell specific manner. Finally, this study provides evidence to suggest that both mature miRNA levels and miRNA target abundance can stabilise miRNA biogenesis and promote pri-miRNA production in the absence of key and auxiliary proteins involved in miRNA biogenesis.

Subjects/Keywords: microRNAs (miRNAs); miRNA biogenesis.; RNA binding proteins.; p72 and KHSRP.; Ago2 protein stability.; Dicer.; pri-miRNA.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Connerty, P. P. (2016). Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins. (Thesis). University of Technology, Sydney. Retrieved from http://hdl.handle.net/10453/90062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Connerty, Patrick Peter. “Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins.” 2016. Thesis, University of Technology, Sydney. Accessed January 25, 2020. http://hdl.handle.net/10453/90062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Connerty, Patrick Peter. “Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins.” 2016. Web. 25 Jan 2020.

Vancouver:

Connerty PP. Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins. [Internet] [Thesis]. University of Technology, Sydney; 2016. [cited 2020 Jan 25]. Available from: http://hdl.handle.net/10453/90062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Connerty PP. Investigating the regulation of miRNA biogenesis and Argonaute2 by RNA binding proteins. [Thesis]. University of Technology, Sydney; 2016. Available from: http://hdl.handle.net/10453/90062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Kent State University

3. Mirihana Arachchilage, Gayan S. REGULATORY ROLES OF G-QUADRUPLEX IN microRNA PROCESSING AND mRNA TRANSLATION.

Degree: PhD, College of Arts and Sciences / Department of Chemistry, 2016, Kent State University

G-quadruplexes (GQs) are secondary structures that can be adopted by both DNA and RNA in the presence of monovalent cations and they are known to play important regulatory roles in a wide range of biological processes, such as, transcription, translation, splicing, mRNA localization, and telomere homeostasis. Although the functional roles of GQ structures have been extensively studied, the evolution of GQ structure is poorly understood. Thus, we investigated the evolutionary selection of GQ structures within the codon region (CDS) of mRNAs in a wide range of species and observed that the stable GQs are selected against within CDSs by synonymous codon usage. Furthermore, our results revealed context-dependent codon bias against the formation of stable GQs at the codon level resolution, thus delineating the evolutionary mechanism of GQ selection.Although a myriad of studies has reported the regulatory roles of GQs that are present in mRNAs, very little is known about the prevalence and functions of GQs in non-coding RNAs. We revealed the presence of GQ structures in precursor microRNA (pre-miRNA) and showed a regulatory role for GQs in miRNA biogenesis. Using a clinically important miRNA (miR-92b), we showed the existence of an equilibrium between GQ and the canonical stem-loop conformation which can regulate various stages of miRNA biogenesis such as nuclear export and Dicer-mediated maturation. Furthermore, we demonstrated that GQ structures can potentially be targeted in pre-miRNAs to treat diseases in which corresponding miRNAs are overexpressed. We showed that a rationally designed locked nucleic acid (LNA) oligonucleotide, which specifically binds with the GQ confirmation containing pre-miRNA can be used to treat non-small cell lung cancer where miR-92b is overexpressed.Although many different GQ binding ligands have been developed as therapeutics, the selectivity of these ligands is crucial to estimate the off-target effects. We developed an <i>in vitro </i>library screening approach to evaluate the selectivity of such ligands before proceeding into more detailed path of therapeutic development. Collectively, results from this set of studies not only elaborate our understanding of the structure-function relationship of RNAs and its clinical importance but also provide insight into the evolutionary selection of RNA secondary structures as regulatory elements. Advisors/Committee Members: Basu, Soumitra (Advisor).

Subjects/Keywords: Biochemistry; Cellular Biology; Chemistry; Molecular Biology; G-quadruplex; Dicer; pre-miRNA; microRNA; Codon bias; translation; microRNA biogenesis; library screening; LNA; lung cancer; RNA; RNA secondary structure; RNA switch; locked nucleic acids; miRNA therapeutics; in vitro selection; GQ switch

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Mirihana Arachchilage, G. S. (2016). REGULATORY ROLES OF G-QUADRUPLEX IN microRNA PROCESSING AND mRNA TRANSLATION. (Doctoral Dissertation). Kent State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=kent1469576783

Chicago Manual of Style (16th Edition):

Mirihana Arachchilage, Gayan S. “REGULATORY ROLES OF G-QUADRUPLEX IN microRNA PROCESSING AND mRNA TRANSLATION.” 2016. Doctoral Dissertation, Kent State University. Accessed January 25, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1469576783.

MLA Handbook (7th Edition):

Mirihana Arachchilage, Gayan S. “REGULATORY ROLES OF G-QUADRUPLEX IN microRNA PROCESSING AND mRNA TRANSLATION.” 2016. Web. 25 Jan 2020.

Vancouver:

Mirihana Arachchilage GS. REGULATORY ROLES OF G-QUADRUPLEX IN microRNA PROCESSING AND mRNA TRANSLATION. [Internet] [Doctoral dissertation]. Kent State University; 2016. [cited 2020 Jan 25]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1469576783.

Council of Science Editors:

Mirihana Arachchilage GS. REGULATORY ROLES OF G-QUADRUPLEX IN microRNA PROCESSING AND mRNA TRANSLATION. [Doctoral Dissertation]. Kent State University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1469576783

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