RNA structure mediated thermoregulation: What can we learn from plants?

Abstract

RNA molecules have the capacity to form a multitude of distinct secondary and tertiary structures, but only the most energetically favorable conformations are adopted at any given time. Formation of such structures strongly depends on the environment and consequently, these structures are highly dynamic and may refold as their surroundings change. Temperature is one of the most direct physical parameters that influence RNA structure dynamics, and in turn, thermosensitive RNA structures can be harnessed by a cell to perceive and respond to its temperature environment. Indeed, many thermosensitive RNA structures with biological function have been identified in prokaryotic organisms, but for a long time such structures remained elusive in eukaryotes. Recent discoveries, however, reveal that thermosensitive RNA structures are also found in plants, where they affect RNA stability, pre-mRNA splicing and translation efficiency in a temperature-dependent manner. In this minireview, we provide a short overview of thermosensitive RNA structures in prokaryotes and eukaryotes, highlight recent advances made in identifying such structures in plants and discuss their similarities and differences to established prokaryotic RNA thermosensors.

Keywords: RNA structure; plants; protein synthesis; temperature; thermosensor; translation.

FIGURE 1

Comparison of the proposed plant RNA ThermoSwitch mechanism (A,B) with that of known Prokaryotic thermometers (C,D). (A) The plant RNA ThermoSwitch adopts a closed conformation at temperatures below 22°C, at which cap-dependent recruitment of 43S complex occurs, however further scanning and identification of the start codon is impeded by the ThermoSwitch. (B) When temperature reaches between 27 and 32°C, the ThermoSwitch RNA undergoes reversible partial melting, thereby adopting a relaxed conformation and allowing the 43S complex to precede scanning. The partially open conformation temporarily impedes further incoming scanning subunits until the preceding 43S complex encounters the start codon with sufficient initiation context, thereby facilitating 48S initiation complex formation followed by recruitment of the 60S ribosomal subunit. Thus, the switch from closed (<22°C) to relaxed conformation at 27-32°C may enhance translation whereby translation initiation rates are selectively increased at higher temperatures (Chung et al., 2020). The fully mature 80S ribosomes then enter the elongation stage of translation allowing protein synthesis, by which time (∼minutes) the ThermoSwitch RNA fully melts accompanied by the helicase activity of incoming scanning 43S complexes. It is also possible that the ThermoSwitch recruits an RNA binding protein, either at the stable conformation to further stabilise the ThermoSwitch at lower temperature (<22°C), or at the relaxed conformation to enhance 43S scanning. (C) The prokaryotic RNA thermometers operate by a distinct mechanism, since translation initiation here is dependent on the direct interaction of 16S rRNA within the 30S ribosomal subunit and the SD-sequence. The bacterial RNA thermosensors are typically located very close to the start codon and encompass the SD sequence preventing access to the initiating small ribosomal subunit. (D) At higher temperatures (>37°C), the RNA secondary structure either melts (e.g., ROSE element) or switches into an alternative structure (e.g., CspA cold shock transcript); both processes relieve the SD sequence from intra-molecular base pairing to allow interactions with the 30S ribosomal subunit and recruitment of 50S ribosomal subunit (Kortmann and Narberhaus, 2012). The fully assembled 70S ribosomes then proceed to elongation. Thus, translational induction mediated by prokaryotic RNA thermometers in cis is generally proportional to temperature: the higher the temperature, the less stable is the respective RNA secondary structure and therefore the more efficient is translation initiation. In both instances, translation initiation occurs within seconds of temperature rise while entry into elongation and complete protein synthesis may occur within minutes.