RNA synthesis and purification: RNAs 1b-g were synthesized on a MerMade 6 DNA/RNA synthesizer at 1 µmol scale using standard phosphoramidite chemistry. 2'-Ac-Ac-C-succinyl-CPG was used as the solid support. Deblocking: TCA (2% in DCM), 9 sec × 3. Coupling: 5'-ODMTr, 2'-OTBDMS, CE-phosphoramidites of Bz-A, Ac-C, Ac-G, U, Ψ (for 1c), Ac-m 5 C (for 1d, 2'-TOM instead of 2'-OTBDMS), Pac-m 6 A (for 1e) and Cl-Ac-m 1 A (for 1f) (0.1 M in ACN), Bz-m 3 C (for 1g) (0.125 M in ACN), 5-(ethylthio)-1H-tetrazole (ETT, 0.25 M in ACN), 6 min × 3 except for m 1 A (15 min × 3) and m 3 C (12 min × 3). Capping: Cap A THF/pyridine/Ac 2 O, Cap B Melm (16% in THF), 50 sec × 3. Oxidation: I 2 (0.1 M in THF/pyridine/H 2 O), 40 sec × 3. Cleavage and removal of nucleobase protection groups: For 1b-e, the CPG was treated with the mixture of 28% NH 4 OH and 40% CH 3 NH 2 (1:1 v/v), 65 o C, 20 min. The supernatant was transferred to a clean centrifuge tube, and the CPG was washed with water. For 1f, the CPG was treated with the solution of NH 3 in CH 3 OH (2.0 M), rt, 60 h. The supernatant was transferred to a clean centrifuge tube, and the CPG was washed with a solution of ammonia in CH 3 OH (2.0 M). For 1g, the CPG was treated with 28% NH 4 OH at rt for 16 h. The supernatant was transferred to a clean centrifuge tube, and the CPG was washed with water. For 1a-g, the supernatant and the washes were combined, and volatiles were evaporated using a vacuum centrifugal evaporator. Removal of 2'-OH protecting groups: For 1a-g, the RNA was dissolved in DMSO (115 µL). The mixture was heated at 65 o C for 5 min if RNA was not dissolved completely. Triethylamine (TEA, 60 µL) was added. After mixing, TEA-3HF (75 µL) was added. The mixture was heated at 65 o C for 2.5 h. After cooling on ice, Glen-Pak RNA Quenching Buffer (1.75 mL) was added. After mixing, the quenched RNA solution was loaded on a Glen-Pak™ RNA purification cartridge that was preconditioned using ACN (0.5 mL) followed by TEAA (2 M, 1.0 mL). The cartridge was washed sequentially with the mixture of ACN and 2 M TEAA solution (1:9 v/v, pH 7.0, 1.0 mL), RNase free water (1.0 mL), TFA (2%, 1.0 mL × 2, 5'-ODMTr deprotection), and deionized water (1.0 mL × 2). The fully deprotected RNA was then eluted with the solution of 0.1 M NH 4 HCO 3 in 30% ACN (1.0 mL). The solution was evaporated to dryness and analyzed with RP HPLC using conditions described elsewhere. All RNAs were desalted using RP HPLC or the dissolve-spin method and characterized using MALDI MS.