Experimental Validation of Predicted Mammalian MicroRNAs of Mirtron Origin

Schamberger, Anita; Orbán, Tamás I.

doi:10.1007/978-1-4939-1062-5_22

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…Those fundamental questions remain unaddressed. Through advances in technologies [ 114 , 115 , 116 ], development of new strategies [ 117 , 118 , 119 , 120 , 121 , 122 , 123 ], and establishment of databases for sharing information [ 124 , 125 , 126 ], hopefully those questions will be addressed in the near future.…”

Section: Discussionmentioning

confidence: 99%

Coupling and Coordination in Gene Expression Processes with Pre-mRNA Splicing

Pan¹,

Lee²,

Huang³

et al. 2015

IJMS

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RNA processing is a tightly regulated and highly complex pathway which includes transcription, splicing, editing, transportation, translation and degradation. It has been well-documented that splicing of RNA polymerase II medicated nascent transcripts occurs co-transcriptionally and is functionally coupled to other RNA processing. Recently, increasing experimental evidence indicated that pre-mRNA splicing influences RNA degradation and vice versa. In this review, we summarized the recent findings demonstrating the coupling of these two processes. In addition, we highlighted the importance of splicing in the production of intronic miRNA and circular RNAs, and hence the discovery of the novel mechanisms in the regulation of gene expression.

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Section: Discussionmentioning

confidence: 99%

Coupling and Coordination in Gene Expression Processes with Pre-mRNA Splicing

Pan¹,

Lee²,

Huang³

et al. 2015

IJMS

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“…For the expression of artificial mirtrons, oligonucleotides corresponding to the sense and antisense sequence of the specific mirtrons were hybridized to form a double-stranded DNA, then inserted as an artificial intron into the PvuII site of EGFPm by blunt-end ligation [ 39 , 48 ]. As a control, we used the third intron of the mouse IgCε gene [ 49 ] or a canonical intronic miRNA (mir-33b), as we described earlier [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

Posttranscriptional Regulation of the Human ABCG2 Multidrug Transporter Protein by Artificial Mirtrons

Schamberger

Várady

Fóthi

et al. 2021

Genes

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ABCG2 is a membrane transporter protein that has been associated with multidrug resistance phenotype and tumor development. Additionally, it is expressed in various stem cells, providing cellular protection against endobiotics and xenobiotics. In this study, we designed artificial mirtrons to regulate ABCG2 expression posttranscriptionally. Applying EGFP as a host gene, we could achieve efficient silencing not only in luciferase reporter systems but also at the ABCG2 protein level. Moreover, we observed important new sequential-functional features of the designed mirtrons. Mismatch at the first position of the mirtron-derived small RNA resulted in better silencing than full complementarity, while the investigated middle and 3′ mismatches did not enhance silencing. These latter small RNAs operated most probably via non-seed specific translational inhibition in luciferase assays. Additionally, we found that a mismatch in the first position has not, but a second mismatch in the third position has abolished target mRNA decay. Besides, one nucleotide mismatch in the seed region did not impair efficient silencing at the protein level, providing the possibility to silence targets carrying single nucleotide polymorphisms or mutations. Taken together, we believe that apart from establishing an efficient ABCG2 silencing system, our designing pipeline and results on sequential-functional features are beneficial for developing artificial mirtrons for other targets.

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“…Interestingly, however, hundreds of microRNAs have been found to derive from the intronic regions of coding genes [ 114 , 115 ]. The maturation of these intronic microRNAs has been suggested to depend mainly on the splicing machinery instead of the commonly used Drosha/DGCR8 complex [ 116 , 117 , 118 , 119 ]. This genic source of microRNA implies correlations between AS and microRNA-mediated gene regulations.…”

Section: Alternative 3'utr and Microrna-mediated Gene Regulation Imentioning

confidence: 99%

“…Dysregulation of protein–protein interactions (PPIs) plays a critical role in tumorigenesis [ 119 , 143 ]. Indeed, PPI network analyses have been used to unravel the molecular mechanism of carcinogenesis [ 144 ], to identify drug targets for cancer therapy [ 145 ], and to characterize drug-regulated genes [ 146 ].…”

Section: Rna Splicing and Protein Interactions In Cancermentioning

confidence: 99%

Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis

Chen

2014

IJMS

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Alternative RNA structures (ARSs), or alternative transcript isoforms, are critical for regulating cellular phenotypes in humans. In addition to generating functionally diverse protein isoforms from a single gene, ARS can alter the sequence contents of 5'/3' untranslated regions (UTRs) and intronic regions, thus also affecting the regulatory effects of these regions. ARS may introduce premature stop codon(s) into a transcript, and render the transcript susceptible to nonsense-mediated decay, which in turn can influence the overall gene expression level. Meanwhile, ARS can regulate the presence/absence of upstream open reading frames and microRNA targeting sites in 5'UTRs and 3'UTRs, respectively, thus affecting translational efficiencies and protein expression levels. Furthermore, since ARS may alter exon-intron structures, it can influence the biogenesis of intronic microRNAs and indirectly affect the expression of the target genes of these microRNAs. The connections between ARS and multiple regulatory mechanisms underline the importance of ARS in determining cell fate. Accumulating evidence indicates that ARS-coupled regulations play important roles in tumorigenesis. Here I will review our current knowledge in this field, and discuss potential future directions.

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Experimental Validation of Predicted Mammalian MicroRNAs of Mirtron Origin

Cited by 4 publications

References 30 publications

Coupling and Coordination in Gene Expression Processes with Pre-mRNA Splicing

Coupling and Coordination in Gene Expression Processes with Pre-mRNA Splicing

Posttranscriptional Regulation of the Human ABCG2 Multidrug Transporter Protein by Artificial Mirtrons

Alternative RNA Structure-Coupled Gene Regulations in Tumorigenesis

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