Context-specific effects of sequence elements on subcellular localization of linear and circular RNAs

Area of Science:

• Molecular Biology
• RNA Biology
• Post-transcriptional Regulation

Background:

• Long noncoding RNAs exhibit diverse post-transcriptional fates.
• Short sequence elements are known to influence RNA behavior.
• Understanding these elements is crucial for comprehending gene regulation.

Purpose of the Study:

• To investigate how noncoding RNA-derived sequences affect the subcellular localization and stability of circular and linear RNAs.
• To determine the role of specific RNA-binding proteins in mediating these sequence-dependent effects.
• To elucidate the combinatorial mechanisms governing long RNA post-transcriptional fates.

Main Methods:

• Utilized massively parallel RNA assays.
• Analyzed both circular and linear RNA forms, including spliced and unspliced variants.
• Investigated the impact of specific sequence elements and RNA-binding protein interactions.

Main Results:

• Sequence element effects are highly dependent on the host RNA context.
• Limited overlap exists in sequences promoting nuclear enrichment for linear versus circular RNAs.
• SRSF1, SAFB, and IGF2BP1 binding differentially regulate RNA localization and splicing status.

Conclusions:

• The post-transcriptional fate of long RNAs is determined by a combination of sequence elements, splicing status, and RNA structural features.
• RNA-binding proteins play key roles in mediating sequence-specific regulatory outcomes.
• Context-dependent interactions are critical for precise control over RNA localization and stability.