Diverse intrinsic properties shape transcript stability and stabilization in Mycolicibacterium smegmatis

Area of Science:

• Molecular Biology
• Microbiology
• Bioinformatics

Background:

• Mycobacteria adapt to environmental stress by regulating transcript degradation.
• The specific mechanisms controlling messenger RNA (mRNA) stability in mycobacteria remain largely unknown.
• Understanding mRNA stability is crucial for deciphering bacterial adaptation strategies.

Purpose of the Study:

• To investigate the mechanisms controlling mRNA stability in mycobacteria.
• To identify transcript properties associated with transcript stability and stress-induced stabilization.
• To understand how growth conditions and transcript type influence mRNA half-lives.

Main Methods:

• Measured genome-wide mRNA half-lives in *Mycolicibacterium smegmatis* during log-phase growth and hypoxia-induced growth arrest.
• Developed machine learning models to identify non-linear relationships between transcript properties and stability.
• Analyzed transcript properties, including leadered and leaderless transcripts, under different growth conditions.

Main Results:

• The transcriptome was globally stabilized under hypoxic conditions.
• Essential gene transcripts were generally more stabilized than non-essential gene transcripts during stress.
• Machine learning models identified distinct transcript properties predictive of half-life in log phase versus hypoxia, varying between leadered and leaderless transcripts.

Conclusions:

• Transcript properties are differentially associated with transcript stability based on transcript type and growth conditions.
• A complex interplay exists between transcript features and the microenvironment in shaping transcript stability in mycobacteria.
• These findings provide insights into the regulatory mechanisms of mRNA stability for bacterial adaptation.