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Is Messenger RNA Regulation Controlled by an Irreducibly Complex Pathway?

What we know about the complexity of the cellular information storage, processing and retrieval mechanisms continues to increase exponentially, and at an unprecedented rate. Almost on a daily basis, new papers are published revealing the ingenuity of the elaborate mechanisms by which the cell processes information -- processes and mechanisms that bespeak design and continue to elude explanation by Darwinian means. For how exactly could such a system - apparently, an irreducibly complex one - be accounted for in terms of traditional Darwinian selective pressure?

A new paper has just been published in Molecular Cell, in which the researchers, Karginov et al. reported their discovery that messenger RNA (mRNA) can be targeted for destruction by several different molecules.

According to the paper's summary,

The life span of a mammalian mRNA is determined, in part, by the binding of regulatory proteins and small RNA-guided complexes. The conserved endonuclease activity of Argonaute2 requires extensive complementarity between a small RNA and its target and is not used by animal microRNAs, which pair with their targets imperfectly. Here we investigate the endonucleolytic function of Ago2 and other nucleases by transcriptome-wide profiling of mRNA cleavage products retaining 5′ phosphate groups in mouse embryonic stem cells (mESCs). We detect a prominent signature of Ago2-dependent cleavage events and validate several such targets. Unexpectedly, a broader class of Ago2-independent cleavage sites is also observed, indicating participation of additional nucleases in site-specific mRNA cleavage. Within this class, we identify a cohort of Drosha-dependent mRNA cleavage events that functionally regulate mRNA levels in mESCs, including one in the Dgcr8 mRNA. Together, these results highlight the underappreciated role of endonucleolytic cleavage in controlling mRNA fates in mammals.

Translated into English, the paper makes the following points:

  • RNA interference (RNAi) refers to a cellular pathway that helps to regulate the activity of genes within the cell. Fundamental to the process of RNA interference are small interfering RNAs (siRNA) and microRNAs (MiRNA).

  • Small RNAs can prevent the translation of a target messenger RNA into protein, thereby reducing the activity of the RNAs to which it binds.

  • MicroRNAs also act as regulators, binding to their complementary sequences on a target messenger RNA to result in gene silencing. MiRNAs also serve as guides to a family of proteins called Artonautes. When a miRNA-Artonaute complex binds to its complementary mRNA target, it triggers its destruction.

  • The researchers surveyed a population of cleaved mRNAs in mammalian embryonic stem cells, discovering that mRNAs had been sliced or cleaved by the enzyme Ago2 and other enzymes.

  • It was previously thought that the destruction was due to the destabilization of mRNA by initiation of cellular pathways. In contrast, Karginov et al. have discovered a host of ways that mRNA may be destroyed by enzymatic cleavage.
  • So, how exactly can these things be explained by traditional Darwinian selective pressure?

    Consider, for example, the enzyme Dicer, which is responsible for activating the RNAi pathway. The pathway is initiated when Dicer cleaves long double-stranded RNA (dsRNA) molecules into shorter fragments, consisting of roughly 20 nucleotides each. Each fragment possesses two strands, one of which (called the "guide strand") is subsequently incorporated into the "RISC complex" (RNA-induced silencing complex). Following base pairing between the guide strand and its complementary sequence, a cleavage is brought about by the enzyme Argonaute.

    One has to wonder whether there is any significant biological system that, in fact, can be accounted for in a Darwinian step-wise fashion. The adequacy of Darwinian selection to account for the features of biodiversity is never demonstrated. Rather, it is merely assumed that Darwinism can account for these systems, in the almost complete absence of corroborative data.

    It might be asked of the Darwinian advocates what kind of system, in principle, could not be explained in Darwinian fashion. In the absence of such testable statements, Darwinism cannot be regarded as good falsifiable science.