Lecture 4: Regulatory noncoding RNAs — Key Concepts

RNA interference overview

  • RNA interference (RNAi) is the regulation of gene expression by targeting mRNA molecules for degradation triggered by double-stranded RNA.

Small interfering RNAs (siRNAs)

  • Length: 21−25nt21-25 \mathrm{nt}

  • Double-stranded RNA is cleaved by the Dicer enzyme into siRNAs.

  • One strand of siRNA is loaded into the RNA-induced silencing complex (RISC).

  • RISC pairs with mRNA from the same gene the siRNA originated from with perfect base pairing, leading to cleavage and degradation of the mRNA.

MicroRNAs (miRNAs)

  • Length: 21−25nt21-25 \mathrm{nt}

  • Derived from transcription of hairpin precursors; Dicer removes the terminal loop to produce mature miRNA.

  • RISC carries the miRNA guide; binding to target mRNA is usually imperfect, resulting in translational repression and often mRNA degradation.

Primary miRNA processing

  • Pri-miRNA is transcribed and forms a hairpin structure.

  • Processing by Dicer and associated factors yields mature miRNA that loads into RISC.

  • RISC-miRNA pairs with mRNA targets (often multiple) via imperfect base pairing to regulate expression.

Comparison: siRNA vs miRNA

  • Origin: siRNA from double-stranded RNA; miRNA from hairpin precursors.

  • Base-pairing: siRNA typically full (perfect) base pairing; miRNA often imperfect.

  • Target set: siRNA tends to target the same gene’s mRNA; miRNA can target multiple genes.

Piwi-interacting RNAs (piRNAs)

  • Length: 24−31nt24-31 \mathrm{nt}

  • Derived from long single-stranded RNA; not processed by Dicer.

  • Associate with Piwi proteins.

  • Function: suppress transposon expression/movement in germ cells; also present in somatic tissue with less defined roles.

Long noncoding RNAs (lncRNAs)

  • Length: typically >200nt200 \mathrm{nt}

  • Lack an open reading frame (no protein-coding potential).

  • Have a 5′ cap and a 3′ poly(A) tail; undergo splicing like mRNA.

  • Diverse regulatory roles: interact with transcription factors, act as decoys for miRNAs, modify chromatin structure.

Regulatory ncRNAs: key takeaway

  • Regulatory ncRNAs include miRNAs, piRNAs, lncRNAs (and circRNAs) and regulate gene expression at multiple post-transcriptional levels.

  • Sizes and processing details are distinct (Dicer-dependent vs. -independent pathways) but converge on controlling mRNA fate and translation.