UltraMarathonRT: When Your Reverse Transcription Must Go Long

Why It Matters

The enzyme’s superior processivity and structure‑unwinding capability enable more complete and accurate long‑read RNA data, accelerating research into complex splicing events and expanding the utility of nanopore sequencing in both discovery and clinical settings.

Key Takeaways

• UltraMarathonRT transcribes >30 kb RNA at 30 °C
• Provides helicase activity, reducing secondary‑structure stalls
• Yields 67% more >10 kb reads vs Induro
• Detects ~2× more retained introns in UHRR
• Enables template switching with three‑adenine overhang

Pulse Analysis

The field of reverse transcription has long been dominated by enzymes derived from retroviruses—Avian Myeloblastosis Virus (AMV) and Moloney Murine Leukemia Virus (MMLV). While reliable for cDNA synthesis, these enzymes lack intrinsic helicase activity and often stall on RNA templates with strong secondary structures, limiting read length and fidelity. UltraMarathonRT, released by Connecticut‑based RNAConnect, breaks this paradigm by harnessing a prokaryotic group II intron‑encoded polymerase. The enzyme exhibits exceptional processivity, routinely copying transcripts longer than 30 kilobases, and operates optimally at 30 °C, a temperature that preserves RNA integrity while still providing the unwinding power absent in traditional RTs.

RNAConnect’s new kit couples UltraMarathonRT with Oxford Nanopore’s direct‑RNA sequencing workflow, delivering a measurable boost in long‑read performance. In head‑to‑head tests against NEB’s Induro, the UltraMarathonRT kit generated 67 % more reads exceeding 10 kb, 24 % more reads over 5 kb, and an 11 % increase for reads longer than 2 kb. The enzyme’s built‑in helicase smooths complex secondary structures, improving the capture of long non‑coding RNAs such as the 17‑kb XIST transcript. As PacBio and ONT platforms continue to lower cost per base, these gains translate directly into deeper, more comprehensive transcriptome maps.

The ability to faithfully traverse full‑length transcripts reshapes how researchers interrogate alternative splicing, poison exons, and detained introns—regulatory features increasingly linked to disease. UltraMarathonRT has already shown roughly double the detection rate of retained introns in universal human reference RNA, suggesting that many hidden splicing events may become visible with routine use. By simplifying library preparation and delivering higher‑quality long reads, the kit positions RNAConnect as a strategic player in the growing RNA‑sequencing market, where accurate, ultra‑long reads are becoming essential for both basic biology and clinical diagnostics.