Planting the seed: target recognition of short guide RNAs

• Seed sequences are present in small RNA-guided gene regulatory and immune systems.
• The seed enables a rapid target search by RNA-guided complexes.
• Proteins such as Argonaute, Cascade, and Cas9 are essential for seed functioning.
• Seed sequences contribute to the evolution of complex gene regulatory networks.

Small guide RNAs play important roles in cellular processes such as regulation of gene expression and host defense against invading nucleic acids. The mode of action of small RNAs relies on protein-assisted base pairing of the guide RNA with target mRNA or DNA to interfere with their transcription, translation, or replication. Several unrelated classes of small noncoding RNAs have been identified including eukaryotic RNA silencing-associated small RNAs, prokaryotic small regulatory RNAs (sRNAs), and prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats) RNAs (crRNAs). All three groups identify their target sequence by base pairing after finding it in a pool of millions of other nucleotide sequences in the cell. In this complicated target search process, a region of 6–12 nucleotides (nt) of the small RNA termed the ‘seed’ plays a critical role. We review the concept of seed sequences and discuss its importance for initial target recognition and interference.