How do microRNAs recognize their targets?

Sites with as little as seven base pairs matching the miRNA 5′ end can confer regulation; such 5′-dominant sites are common in conserved 3′ UTRs.

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How short can a functional miRNA site be?

As little as seven base-pairs to the miRNA 5′ end.

Where do 5′ dominant sites occur more often?

In conserved 3′ UTR sequences.

How enriched vs random?

2- to 3-fold more often than expected at random.

Why were many sites overlooked?

Limited pairing capacity ranked low in overall pairing-energy methods.

What do miRNAs do?

Post-transcriptional regulation by binding complementary sites on target mRNAs.

About what fraction of animal genes are miRNAs?

Approximately 1%.

What evidence types support the principles?

Experimental and computational evidence.

What ranking problem hurts energy-only searches?

Short 5′ sites rank low when optimizing overall pairing energy.

Are 7-bp sites biologically used?

Yes—used in biologically relevant targets in vivo.

Student takeaway?

Seed pairing at the miRNA 5′ end is a core targeting rule.