Our Target & MoA — Structured RNA and Three Control Modes

++OUR TARGETSTRUCTURED RNA / SPLICING REGULATION

Two targets for small molecules

RNA is not only a message. Its sequence folds into stems, loops and higher-order motifs that create addressable surfaces, and the same transcript is assembled through splice decisions that set which isoform a cell makes. Those are two targets, not one. We hold both to the same three questions: is the target addressable, does engaging it change biology, and can it be told apart from everything nearby.

TARGET A

Structured RNA

PLATFORM · MatrixFOREST

STRUCTURE

Folding creates addressable surfaces

Sequence alone is flat. Folded RNA presents bulges, internal loops and junctions with geometry a small molecule can recognize.

FUNCTION

One element can redirect the whole transcript

Structural elements govern decay, translation and localization. Engaging one shifts the fate of the whole message, not a single protein interaction.

SELECTIVITY

Shape separates what sequence cannot

Short motifs recur throughout the transcriptome. Three-dimensional context is what distinguishes the intended site from the rest.

TARGET B

Splicing regulation

PLATFORM · SpliceVerse

STRUCTURE

Splice decisions run through defined elements

Splice sites, branch points and the regulatory elements around them are discrete, already mapped and structurally constrained: a finite set of places to act.

FUNCTION

A discrete switch with a direct readout

Exon inclusion moves between defined states, so the effect of binding is read as an isoform ratio rather than a proxy signal.

SELECTIVITY

The transcript stays under native control

Shifting a splice decision acts on the endogenous gene, in its own locus and under its own promoter. Expression is redirected, not replaced.

COMMON INPUT STRUCTURED RNA /
SPLICING COMPLEX SELECTIVE SMALL-MOLECULE ENGAGEMENT

01CHANGE RNA
ABUNDANCE

02CHANGE ISOFORM
OUTPUT

03TRIGGER RNA
SURVEILLANCE

The diagrams below illustrate mechanism classes. They do not depict a specific target, compound, development program or quantitative result.

++THREE CONTROL MODESSELECT A MECHANISM

Three routes through RNA biology

The initial recognition event can be similar. What changes is the regulatory process being influenced, and therefore the biological output.

MODE 01 / RNA STABILITY CONTROL

Change how long an RNA remains available

Structured regions of RNA can recruit or exclude regulatory proteins that influence transcript stability. Small-molecule engagement can reshape that local interaction environment, shifting the balance between RNA maintenance and decay.

CONTROL POINT: RNA–protein interaction or structural state
RNA-LEVEL EFFECT: Altered transcript half-life and abundance
POSSIBLE OUTPUT: Increase or decrease in protein production

01 / TARGET STRUCTURED RNA A regulatory structure recruits RNA-binding proteins.

SMALL MOLECULE ENGAGES

02 / CONTROL POINT PROTEIN ACCESS CHANGES The local interaction environment is reshaped.

03A / PROTECTEDRNA PERSISTSTranscript remains available

03B / EXPOSEDRNA DECAYSTranscript abundance falls

MODE 02 / SPLICING CONTROL

Change how exons are assembled into an mRNA

Pre-mRNA offers multiple splice choices. By engaging a structured regulatory region, a small molecule can influence splice-site recognition or the activity of splicing factors, favoring one mature isoform over another.

CONTROL POINT: Splice-site recognition and regulatory-factor access
RNA-LEVEL EFFECT: Exon inclusion, exclusion or alternative splice choice
POSSIBLE OUTPUT: A different protein isoform or expression profile

01 / PRE-mRNA ALTERNATIVE EXON CHOICE E2 is regulated before the mature message is assembled.

REGULATORY STRUCTURE ENGAGED

02 / CONTROL POINT SPLICE-SITE RECOGNITION SHIFTS Splicing factors favor inclusion or exclusion.

03A / EXON INCLUDEDISOFORM AE1 · E2 · E3

03B / EXON SKIPPEDISOFORM BE1 · E3

MODE 03 / POISON EXON INCLUSION

Introduce a stop signal that routes the RNA toward decay

A poison exon is a normally regulated exon that can introduce a premature termination codon when included in the mature transcript. Promoting its inclusion can engage nonsense-mediated mRNA decay, reducing productive mRNA and downstream protein output.

CONTROL POINT: Inclusion of a premature-stop-containing exon
RNA-LEVEL EFFECT: Recognition by nonsense-mediated decay (NMD)
POSSIBLE OUTPUT: Reduced productive transcript and protein output

01 / SPLICING CHOICE POISON EXON IS INCLUDED The mature RNA now contains a premature stop signal.

PREMATURE STOP DETECTED

02 / SURVEILLANCE NMD RECOGNIZES THE TRANSCRIPT Nonsense-mediated decay marks the RNA for removal.

03 / OUTCOME PRODUCTIVE RNA DECREASES Less intact transcript is available for protein production.