Fig. 1

The biogenesis of miRNA, lncRNA, piRNA, circRNA and tRNA-derived fragments. A Several steps are required to produce mature miRNA, including A-to-I nucleotide editing by ADAR, 5’ and 3’ end trimming by Drosha and DGCR8, cleavage of double-stranded precursor miRNA (pre-miRNA) by Dicer through Dicer-dependent pathway or by AGO through Dicer-independent pathway, and finally, formation of miRNA-induced silencing complex (miRISC) with AGO proteins to bind other DNA or RNA targets. Some miRNAs will be modified by the adenosine deaminase (ADAR) proteins which act on double-stranded RNA to do A-to-I editing [148]. Next, two essential enzymes including protein DiGeorge syndrome critical region 8 (DGCR8) and Drosha forms the microprocessor complex and alternatively excise a pre-miRNA and remove the 5’ and 3’ terminals to produce a pre-miRNA duplex [105]. Pre-miRNA duplex in the nucleus is exported to the cytoplasm and is bound by Dicer to cleave the terminal loop to generate a mature miRNA duplex. Therefore, this process produces the isomirs, including 3p, 5p or polymorphic isomirs, which are classified by the arm of their pre-miRNAs [145]. A Genomes transcribed by RNA polymerase II (Pol II) produce mRNA but also lncRNA in both the sense and antisense directions. Most lncRNAs remain in the nucleus, while some of them are exported to the cytoplasm. C The piRNA clusters are a locus that can generate a family of piRNAs from the same single-stranded RNA transcript. PiRNA precursors are cleaved by PIWI proteins. Similar to the AGO protein in miRNAs, PIWI proteins also have three domains: MID, PIWI, and PAZ. D CircRNAs are preferentially generated by the noncanonical head-to-tail splicing of single or multiple exons, a mechanism called “alternative back-splicing (ABS)” by the depleted spliceosome. E Precursor tRNA (pre-tRNA) encoded from the tRNA gene is first trimmed by the endonucleases RNase P and RNase Z at its 5' and 3' ends, forming a cloverleaf-like tertiary structure composed of three stem loops (D loop, anticodon loop, and T loop), undergoing aminoacylation, and ultimately exporting out of the nucleus as a mature tRNA