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Orientation of Human Microprocessor on Primary MicroRNAs
Huong Minh Nguyen1, Trung Duc Nguyen2, Thuy Linh Nguyen2
1Laboratory of Molecular Microbiology, Institute of Biotechnology , Vietnam Academy of Science and Technology , Hanoi , Vietnam.
Abstract:
Single-stranded microRNAs (miRNAs) regulate gene expression by triggering mRNA degradation and/or inhibiting mRNA translation. miRNAs play important roles in various critical cellular processes and are associated with numerous human diseases, including cancer and neurodegenerative diseases. miRNA sequences are embedded in the primary miRNA transcripts (pri-miRNAs) that are initially processed by the Microprocessor complex in the nucleus. Microprocessor can orient itself on pri-miRNAs in two ways: one orientation results in subsequent miRNA production, and the other leads to cleavage of the miRNA sequence. Therefore, orienting Microprocessor on pri-miRNAs is a fundamental mechanism for determining the accuracy and efficiency of pri-miRNA processing and, in turn, miRNA production. Multiple mechanisms controlling Microprocessor orientation on pri-miRNAs, involving both cis-acting RNA elements and trans-acting factors, have recently been revealed. In this review, we discuss these exciting mechanisms and consider potential unknown mechanisms that might regulate Microprocessor orientation on pri-miRNAs.
Insights
MicroRNA (miRNA) production accuracy depends on how the Microprocessor complex orients on pri-miRNAs. Recent discoveries reveal cis-acting RNA elements and trans-acting factors control this crucial orientation mechanism.
Area of Science:
- Molecular Biology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, impacting cellular processes and diseases like cancer.
- miRNA biogenesis involves processing of primary miRNA transcripts (pri-miRNAs) by the Microprocessor complex in the nucleus.
Purpose of the Study:
- To review and discuss the mechanisms controlling Microprocessor complex orientation on pri-miRNAs.
- To explore how this orientation impacts miRNA production accuracy and efficiency.
- To consider potential undiscovered regulatory mechanisms.
Main Methods:
- Literature review of recent findings on Microprocessor orientation.
- Analysis of cis-acting RNA elements involved in pri-miRNA processing.
- Examination of trans-acting factors influencing Microprocessor binding.
Main Results:
- Microprocessor orientation determines whether pri-miRNA processing yields functional miRNAs or leads to cleavage.
- Both RNA sequence/structure (cis-acting) and protein factors (trans-acting) are critical for orienting the Microprocessor.
- Understanding these mechanisms is vital for controlling miRNA levels.
Conclusions:
- Microprocessor orientation is a fundamental regulatory step in miRNA biogenesis.
- Recent advances have elucidated key factors governing this process.
- Further research may uncover novel regulatory pathways for pri-miRNA processing.
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