MicroRNA 3' end nucleotide modification patterns and arm selection preference in liver tissues

Abstract

BackgroundThe expression of microRNA (miRNA) genes undergoes several maturation steps. Recent studies brought new insights into the maturation process, but also raised debates on the maturation mechanism. To understand the mechanism better, we downloaded small RNA sequence reads from NCBI SRA and quantified the expression profiles of miRNAs in normal and tumor liver tissues.ResultsFrom these miRNA expression profiles, we studied several issues related to miRNA biogenesis. First of all, the 3' ends of mature miRNAs usually carried modified nucleotides, generated from nucleotide addition or RNA editing. We found that adenine accounted for more than 50% of all miRNA 3' end modification events in all libraries. However, uracil dominated over adenine in several miRNA types. Moreover, the miRNA reads in the HBV-associated libraries have much lower rates of nucleotide modification. These results indicate that miRNA 3' end modifications are miRNA specific and may differ between normal and tumor tissues. Secondly, according to the hydrogen-bonding theory, the expression ratio of 5p arm to 3p arm miRNAs, derived from the same pre-miRNA, should be constant over tissues. However, a comparison of the expression profiles of the 5p arm and 3p arm miRNAs showed that one arm is preferred in the normal liver tissue whereas the other is preferred in the tumor liver tissue. In other words, different liver tissues have their own preferences on selecting either arm to be mature miRNAs.ConclusionsThe results suggest that besides the traditional miRNA biogenesis theory, another mechanism may also participate in the miRNA biogenesis pathways.

Uridylation and adenylation of RNAs

“…For example, miRNA 3′ uridylation and adenylation exhibit sequence specificity—some miRNAs are predominantly adenylated while others are predominantly uridylated [79,88]. This is consistent with the fact that some nucleotidyl transferases (such as Arabidopsis URT1 and HESO1 and Drosophila Tailor) exhibit a preference for the 3′ nucleotide in its substrate RNA [55,72,73] (Table 1 and Figure 2).…”

“…In GLD2 knockout mice, miR-122 levels were selectively reduced, suggesting that 3′ adenylation stabilizes the miRNA [77]. In human fibroblasts, miR-122 is also monoadenylated and stabilized by GLD2 [78], and the hepatitis B virus may inhibit the process of miR-122 adenylation [79]. Adenylation of miRNAs may have a widespread functional impact in humans, because miRNAs in a variety of human cells are modified by adenylation [77,78,80,81].…”

“…For example, during early development in Drosophila , the levels of uridylated miRNAs are higher, but in mature tissues, the levels of adenylated miRNAs are higher [89]. Patterns of uridylation and/or adenylation of miRNAs in healthy tissues are different from cancerous tissues [79]. …”

Arm Selection Preference of MicroRNA-193a Varies in Breast Cancer

“…Up to now, the arm selection change seems to be attributable to the thermodynamic properties of the miR–miR* duplex. However, numerous studies have reported that the miR#-5p/miR#-3p ratio varies among cell types or during carcinogenesis; therefore, the thermodynamic model alone is insufficient to explain the arm selection change68910111431. Recently, the concept of target-mediated miRNA protection (TMMP) was proposed by Chatterjee et al 31…”

MicroRNA-34 directly targets pair-rule genes and cytoskeleton component in the honey bee

“…This dominant miRNA is typically known as mature miRNA. Nonetheless, the extensive use of next generation sequencing revealed that the dominant arm can differ in different tissues and developmental times678910 in a process called arm switching11. The dominant miRNA is incorporated to RNA-induced silencing complex (RISC) and direct regulation of target-genes through the action of Argonaute (AGO) protein12.…”