Abstract
The biosynthesis pathways of microRNAs (miRNAs) have been well characterized with the identification of the required components. miRNAs are synthesized from the transcripts of miRNA genes and other RNAs, such as introns, transfer RNAs, ribosomal RNAs, small nucleolar RNAs, and even viral miRNAs. These small RNAs are loaded into Argonaute (AGO) proteins and recruit the effector complexes to target mRNAs, repressing their gene expression post-transcriptionally. While mature miRNAs were defined as 19–23 nucleotides (nt), tiny RNAs (tyRNAs) shorter than 19 nt have been found to bind AGOs as equivalent or lesser miRNAs compared to their full-length mature miRNAs. In contrast, my recent study revealed that when human AGO3 loads 14 nt cleavage-inducing tyRNAs (cityRNAs), comprised of the first 14 nt of their corresponding mature miRNA, it can become a comparable slicer to AGO2. This observation raises the possibility that tyRNAs play distinct roles from their mature form. This minireview focuses on human AGO-associated tyRNAs shorter than 19 nt and discusses their possible biosynthesis pathways and physiological benefits, including how tyRNAs could avoid target-directed miRNA degradation accompanied by AGO polyubiquitination.
Highlights
More than 2,000 microRNAs have been reported in humans as of 2019 (Kozomara et al, 2019). miRNAs are varied in sequence, but their lengths fall within a range of 19–23 nucleotides because precursor miRNAs are processed by Dicer, a molecular ruler which generates size-specific miRNA duplexes (Zhang et al, 2004)
After these duplexes are loaded into Argonaute (AGO) proteins, one strand is ejected while the remaining guide strand and AGO form the RNAinduced silencing complex (RISC) (Figure 1A) (Nakanishi, 2016)
Human DICER1 was reported as a Transfer RNAs (tRNAs) slicer (Figure 1B) (Cole et al, 2009), but meta-analysis suggests that the generation of tRNA-derived fragments is DICER1independent because more tRFs were generated in dicer −/− mouse embryonic stem cells (Kumar et al, 2014)
Summary
More than 2,000 microRNAs (miRNAs) have been reported in humans as of 2019 (Kozomara et al, 2019). miRNAs are varied in sequence, but their lengths fall within a range of 19–23 nucleotides (nt) because precursor miRNAs (pre-miRNAs) are processed by Dicer, a molecular ruler which generates size-specific miRNA duplexes (Zhang et al, 2004). MiRNAs are varied in sequence, but their lengths fall within a range of 19–23 nucleotides (nt) because precursor miRNAs (pre-miRNAs) are processed by Dicer, a molecular ruler which generates size-specific miRNA duplexes (Zhang et al, 2004). After these duplexes are loaded into Argonaute (AGO) proteins, one strand is ejected while the remaining guide strand and AGO form the RNAinduced silencing complex (RISC) (Figure 1A) (Nakanishi, 2016). A length of about 22 nt is the hallmark of mature miRNAs (Ambros et al, 2003) This size definition was exploited to eliminate ∼18 nt RNAs during sample preparation or analysis in most early next-generation RNA sequencing (RNA-seq). The discovery has raised the possibility that tyRNAs confer yet-unidentified, but distinct roles on AGOs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
