The article discusses the role of microRNAs (miRNAs) in conferring robustness to biological processes. MiRNAs, which are hairpin-derived RNAs about 20-24 nucleotides long, play a crucial role in post-transcriptional regulation by binding to the 3′ UTR of messenger RNAs (mRNAs) and repressing their expression. They contribute to robustness by reinforcing transcriptional programs, attenuating aberrant transcripts, and suppressing random fluctuations in transcript copy number. The authors highlight several key points: 1. **Coherent Regulation for Precise Developmental Transitions**: MiRNAs often have mutually exclusive RNA expression patterns across tissues, especially in neighboring tissues derived from common progenitors. This helps to reinforce developmental transitions by suppressing residual transcripts from the previous stage. 2. **Cell Fate Switches**: Coherent feed-forward loops (FFLs) involving miRNAs can increase the fidelity of inhibition by acting redundantly. These loops are often used in lineage commitment, where transient fluctuations are counteracted and permanent changes are maintained. 3. **Subtle Repression with Adaptive Impact**: The effect of an individual miRNA on a target's protein level is usually subtle, but multiple sites for a given target can confer stronger repression. This allows miRNAs to dampen fluctuations in gene expression and maintain homeostasis. 4. **Absent and Variable Phenotypes**: Many miRNA knockouts show no gross phenotype, suggesting functional redundancy or compensation mechanisms. However, some phenotypes may only arise under specific conditions or with additional perturbations. 5. **miRNAs as Buffers**: MiRNAs can act as buffers against variation in gene expression by dampening intrinsic and extrinsic noise. Incoherent FFLs can significantly reduce noise in protein output compared to transcriptional repressors. 6. **miRNAs, Robustness, and Evolution**: MiRNAs may contribute to evolvability by potentiating cryptic genetic variation and enhancing canalization, which is the evolved robustness of traits. 7. **Threshold Effects and Endogenous miRNA Competitors**: MiRNA target genes have a threshold below which they are efficiently repressed, and above which they can overwhelm available miRNAs. Competitive endogenous RNAs (ceRNAs) can act as decoys for miRNAs, competing for binding sites. In conclusion, miRNAs are essential for maintaining robustness in biological systems by reinforcing developmental transitions, dampening noise, and contributing to evolvability. Their role in conferring robustness is evident in both normal development and disease states.The article discusses the role of microRNAs (miRNAs) in conferring robustness to biological processes. MiRNAs, which are hairpin-derived RNAs about 20-24 nucleotides long, play a crucial role in post-transcriptional regulation by binding to the 3′ UTR of messenger RNAs (mRNAs) and repressing their expression. They contribute to robustness by reinforcing transcriptional programs, attenuating aberrant transcripts, and suppressing random fluctuations in transcript copy number. The authors highlight several key points: 1. **Coherent Regulation for Precise Developmental Transitions**: MiRNAs often have mutually exclusive RNA expression patterns across tissues, especially in neighboring tissues derived from common progenitors. This helps to reinforce developmental transitions by suppressing residual transcripts from the previous stage. 2. **Cell Fate Switches**: Coherent feed-forward loops (FFLs) involving miRNAs can increase the fidelity of inhibition by acting redundantly. These loops are often used in lineage commitment, where transient fluctuations are counteracted and permanent changes are maintained. 3. **Subtle Repression with Adaptive Impact**: The effect of an individual miRNA on a target's protein level is usually subtle, but multiple sites for a given target can confer stronger repression. This allows miRNAs to dampen fluctuations in gene expression and maintain homeostasis. 4. **Absent and Variable Phenotypes**: Many miRNA knockouts show no gross phenotype, suggesting functional redundancy or compensation mechanisms. However, some phenotypes may only arise under specific conditions or with additional perturbations. 5. **miRNAs as Buffers**: MiRNAs can act as buffers against variation in gene expression by dampening intrinsic and extrinsic noise. Incoherent FFLs can significantly reduce noise in protein output compared to transcriptional repressors. 6. **miRNAs, Robustness, and Evolution**: MiRNAs may contribute to evolvability by potentiating cryptic genetic variation and enhancing canalization, which is the evolved robustness of traits. 7. **Threshold Effects and Endogenous miRNA Competitors**: MiRNA target genes have a threshold below which they are efficiently repressed, and above which they can overwhelm available miRNAs. Competitive endogenous RNAs (ceRNAs) can act as decoys for miRNAs, competing for binding sites. In conclusion, miRNAs are essential for maintaining robustness in biological systems by reinforcing developmental transitions, dampening noise, and contributing to evolvability. Their role in conferring robustness is evident in both normal development and disease states.