MicroRNAs in Chlamydomonas

One of the biggest changes in evolutionary theory in the late 20th century was the growing appreciation for the central role of changes in gene expression in macroevolution. Developmental genes, especially Hox genes, turned out to be remarkably conserved across lineages that diverged over half a billion years ago. The subsequent huge changes in morphology were more often due to changes in when and where those genes were expressed than to changes in the coding sequences of the genes themselves.

Even more recently, an entire new class of regulatory mechanisms was discovered and found to be important in developmental processes. MicroRNAs (miRNAs) are short (21-24 nucleotides) sequences of RNA that reduce gene expression by promoting the breakdown of messenger RNAs (mRNAs) and by repressing translation of mRNAs into proteins. We have only known that microRNAs even existed since the early 1990’s, and their importance in gene regulation and development wasn’t appreciated until the 2000’s.

Although they are structurally similar, plant and animal microRNAs repress gene expression through very different mechanisms. A new paper by Betty Y-W. Chung and colleagues in Nature Plants shows that the regulatory mechanisms of Chlamydomonas microRNAs have both striking similarities and important differences with animal miRNAs:

Here, we provide a comprehensive global analysis of the evolutionarily distant unicellular green alga Chlamydomonas reinhardtii to quantify the effects of miRNA on protein synthesis and RNA abundance. We show that, similar to metazoan steady-state systems, endogenous miRNAs in Chlamydomonas can regulate gene expression both by destabilization of the mRNA and by translational repression. However, unlike metazoan miRNA where target site utilization localizes mainly to 3′ UTRs, in Chlamydomonas utilized target sites lie predominantly within coding regions. These results demonstrate the evolutionarily conserved mode of action for miRNAs, but details of the mechanism diverge between the plant and metazoan kingdoms.

A commentary by Hiro-oki Iwakawa and Yukihide Tomari, in the same issue, has a useful figure that summarizes the mechanisms of plant, animal, and Chlamydomonas microRNAs:

Iwakawa Figure 1

Figure 1 from Iwakawa & Tomari 2017. a, In land plants, microRNA targets are silenced by endonucleolytic cleavage and translational repression generally via a single microRNA binding site, which is extensively complementary to the cognate microRNA. b, In metazoans, microRNAs promote translational repression as well as deadenylation and subsequent messenger RNA decay by guiding RNA-induced silencing complexes to recruit deadenylases and other decay activators to target messenger RNAs via limited complementarity called the seed sequence in the 3′ untranslated region. c, In Chlamydomonas, microRNAs regulate endogenous target messenger RNAs by RNA degradation and/or translational repression via binding to the coding sequence (CDS) with seed complementarity.

So as in both plants and animals, Chlamydomonas microRNAs reduce gene expression by both accelerating the degradation of messenger RNAs and repressing their translation into proteins. Like animal miRNAs, they bind to a target in the messenger RNA that is complementary to only a short section of the miRNA. This differs from plants, in which the target is complementary to the whole miRNA. Like plant miRNAs, the Chlamydomonas version binds to a target in the coding sequence, rather than in the 3′ untranslated region as in animals.

Although this research provides insight into the mechanism of gene regulation by microRNAs in Chlamydomonas, we still don’t know much about its function. In fact, mutations that prevent gene silencing by microRNAs in Chlamydomonas don’t seem to have much effect on the algae:

In this present study, we utilized two silencing mutants raised from our previous forward genetic screen at dcl321 and ago3 (B.Y.-W.C. et al. manuscript in preparation). The dcl3-1 mutant results in almost complete loss of miRNA as well as 21-nucleotide small interfering (si)RNAs whereas ago3-25 is defective in AGO3 that binds to miRNA and is required for translation repression in the reporter system. Neither mutant had obvious growth differences or morphological abnormalities under normal conditions.

Of course, that’s a long way from saying that the microRNAs don’t have important functions. What happens under normal (i.e. ideal) growth conditions in the lab can be very different from the range of conditions an organism might encounter in the wild. It’s still possible that Chlamydomonas microRNAs could play important roles in stress responses, influencing survival under starvation, desiccation, or any number of other sub-optimal conditions.


Stable links:

Chung, B. Y.-W., M. J. Deery, A. J. Groen, J. Howard, and D. Baulcombe. 2017. Endogenous miRNA in the green alga Chlamydomonas regulates gene expression through CDS-targeting. Nature Plants 3:787–794. doi: 10.1038/s41477-017-0024-6

Iwakawa, H., and Y. Tomari. 2017. Silencing messages in a unique way. Nature Plants 3:769–770. doi: 10.1038/s41477-017-0028-2

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