Regulation of small RNA stability: methylation and beyond

Abstract

As central components of RNA silencing, small RNAs play diverse and important roles in many biological processes in eukaryotes. Aberrant reduction or elevation in the levels of small RNAs is associated with many developmental and physiological defects. The in vivo levels of small RNAs are precisely regulated through modulating the rates of their biogenesis and turnover. 2′-O-methylation on the 3′ terminal ribose is a major mechanism that increases the stability of small RNAs. The small RNA methyltransferase HUA ENHANCER1 (HEN1) and its homologs methylate microRNAs and small interfering RNAs (siRNAs) in plants, Piwi-interacting RNAs (piRNAs) in animals, and siRNAs in Drosophila. 3′ nucleotide addition, especially uridylation, and 3′-5′ exonucleolytic degradation are major mechanisms that turnover small RNAs. Other mechanisms impacting small RNA stability include complementary RNAs, cis-elements in small RNA sequences and RNA-binding proteins. Investigations are ongoing to further understand how small RNA stability impacts their accumulation in vivo in order to improve the utilization of RNA silencing in biotechnology and therapeutic applications.

Characterization of the mammalian RNA exonuclease 5/NEF-sp as a testis-specific nuclear 3′ → 5′ exoribonuclease

“…The 10-nt RNA was digested down to at least 7 nt, indicating a minimum length requirement for the ssRNA substrate to reach into the catalytic pocket of the enzyme. The 2 ′ -O-methyl modification on the 3 ′ terminal nucleotide of RNAs is proposed to act as a stabilizing mark by protecting them from exonucleases (Ji and Chen 2012). When hNEFsp was incubated with ssRNA carrying such a 3 ′ end modification, the RNA remained undigested (Fig.…”

Plant MicroRNAs Display Differential 3' Truncation and Tailing Modifications That Are ARGONAUTE1 Dependent and Conserved Across Species

“…The stability and function of small RNAs (sRNAs) are affected by various modifications, such as methylation, uridylation, adenylation, and RNA editing (Kim et al, 2010;Ji and Chen, 2012). Plant microRNAs (miRNAs) pair with their targets near-perfectly and are 39 protected by methylation (Voinnet, 2009); by contrast, animal miRNAs are unmethylated and typically partially complementary to their mRNA targets via the short seed region at the 59 end (Bartel, 2009) and can be truncated and tailed when extensively matched by a target RNA (Ameres et al, 2010).…”

HUA ENHANCER1 Is Involved in Posttranscriptional Regulation of Positive and Negative Regulators in Arabidopsis Photomorphogenesis

“…After being processed from single-stranded RNA hairpin or double-stranded RNAs, miRNAs and small interfering RNAs are stabilized by the action of HUA ENHANCER1 (HEN1), a small RNA methyltransferase that adds a methyl group to the 39-most nucleotide of small RNAs, thus protecting against 39 uridylation and truncation (Ji and Chen, 2012).…”