Biogenesis of telomerase RNA from a protein-coding mRNA precursor

Area of Science:

• Molecular Biology
• Genetics
• RNA Biology

Background:

• Telomerase is crucial for genomic stability and cellular immortality, acting as a ribonucleoprotein (RNP) enzyme.
• The telomerase RNA (TER) component is essential for telomere synthesis, with diverse biogenesis pathways across eukaryotes.
• TERs are typically transcribed by RNA Polymerase III (Pol III) or RNA Pol II, differing in their processing pathways.

Purpose of the Study:

• To investigate the unprecedented messenger RNA (mRNA)-derived biogenesis pathway for telomerase RNA (TER) in the basidiomycete fungus Ustilago maydis.
• To characterize the structural and processing features of the Ustilago maydis TER (UmTER) and its precursor.
• To confirm the mRNA-processing pathway for UmTER production.

Main Methods:

• Bioinformatic analysis of UmTER structure and precursor.
• Characterization of UmTER's 5' end and processing from a larger RNA precursor.
• Expression of a recombinant UmTER precursor from an mRNA promoter.

Main Results:

• The Ustilago maydis TER (UmTER) is a 1,291-nucleotide molecule with a 5'-monophosphate, unlike the TMG cap found in other TERs.
• Mature UmTER is processed from the 3'-untranslated region (3'-UTR) of a larger mRNA precursor containing a 5' m7G cap, introns, and a poly(A) tail.
• The mRNA precursor also encodes the conserved Early meiotic induction protein 1 (Emi1).
• Recombinant UmTER precursor processing confirmed the mRNA-derived biogenesis pathway.

Conclusions:

• Ustilago maydis utilizes a novel mRNA-derived biogenesis pathway for telomerase RNA (TER).
• This pathway involves processing mature TER from the 3'-UTR of a protein-coding mRNA precursor.
• This discovery expands the known mechanisms of TER biogenesis and long noncoding RNA production.