An RNA conformational switch regulates pre-18S rRNA cleavage

Area of Science:

• Molecular Biology
• RNA Biology
• Biochemistry

Background:

• Ribosomal RNAs (rRNAs) are essential components of ribosomes, responsible for protein synthesis.
• The production of mature rRNAs from polycistronic precursors requires precise and ordered enzymatic cleavage events.
• Understanding the regulation of these cleavage steps is crucial for comprehending ribosome biogenesis and function.

Purpose of the Study:

• To elucidate the molecular mechanism governing the order of two critical cleavage steps in 18S ribosomal RNA (rRNA) maturation.
• To identify the RNA elements and conformational changes involved in the processing of pre-18S rRNA.
• To understand the role of RNA structure in regulating RNA-dependent biological processes.

Main Methods:

• In vitro and in vivo RNA structure probing techniques.
• RNA binding and cleavage assays.
• Yeast genetics for studying rRNA processing in a cellular context.

Main Results:

• A conserved RNA sequence within the spacer region between 18S and 5.8S rRNAs interacts with the 18S rRNA decoding site in early intermediates.
• Nucleolar cleavage at site A(2) removes this sequence, inducing a conformational switch in pre-18S rRNA.
• This conformational change facilitates the recruitment of the nuclease Nob1 for subsequent cytoplasmic cleavage and final 18S rRNA maturation.

Conclusions:

• The study reveals a novel mechanism for ordering rRNA cleavage steps through RNA conformational switching.
• This mechanism highlights the intrinsic ability of RNA to regulate biological processes by adopting specific structures.
• The findings provide insights into the fundamental principles of RNA processing and ribosome biogenesis.